Trial Outcomes & Findings for Study for Women and Men With Hormone-receptor Positive Locally Advanced or Metastatic Breast Cancer (NCT NCT03096847)

Last Updated: 2021-10-11

Results Overview

Clinical Benefit Rate (CBR) after 24 weeks of treatment as defined by RECIST 1.1 as percentage of patients with Complete Response (CR), Partial response (PR) or Stable disease (SD) lasting 24 weeks or longer as well as patients with Non-complete response, nonprogressive disease (NCRNPD).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

502 participants

Primary outcome timeframe

At 24 weeks after last patient enrolled in trial

Results posted on

2021-10-11

Participant Flow

504 participants were entered into the study, but 2 of these participants were not treated. The full analysis set is comprised of the 504 participants minus 17 participants, whose data were removed because of inspection findings, to equal 487 participants. This full analysis set includes the 2 participants who were entered into the study but were not treated. 502 participants were treated; these 502 participants are included in the safety set.

Participant milestones

Participant milestones
Measure	Ribociclib + Letrozole Cohort A postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.	Ribociclib + Letrozole Cohort B1 premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B2 premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly
Overall Study STARTED	319	26	157
Overall Study Full Analysis Set	307	26	154
Overall Study COMPLETED	100	6	19
Overall Study NOT COMPLETED	219	20	138

Reasons for withdrawal

Reasons for withdrawal
Measure	Ribociclib + Letrozole Cohort A postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.	Ribociclib + Letrozole Cohort B1 premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B2 premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly
Overall Study Other	2	1	2
Overall Study Lost to Follow-up	1	0	1
Overall Study Death	6	0	2
Overall Study Protocol Violation	3	0	6
Overall Study Physician Decision	12	2	8
Overall Study Withdrawal by Subject	24	1	12
Overall Study Adverse Event	72	6	28
Overall Study Progressive disease	97	10	78
Overall Study Non-compliance with study medication	1	0	0
Overall Study New therapy for study indication	1	0	1

Baseline Characteristics

Study for Women and Men With Hormone-receptor Positive Locally Advanced or Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ribociclib + Letrozole Cohort A n=319 Participants postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.	Ribociclib + Letrozole Cohort B1 n=26 Participants premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B2 n=157 Participants premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Total n=502 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	143 Participants n=5 Participants	26 Participants n=7 Participants	87 Participants n=5 Participants	256 Participants n=4 Participants
Age, Categorical >=65 years	176 Participants n=5 Participants	0 Participants n=7 Participants	70 Participants n=5 Participants	246 Participants n=4 Participants
Age, Continuous	65.7 Years STANDARD_DEVIATION 10.1 • n=5 Participants	46.5 Years STANDARD_DEVIATION 4.9 • n=7 Participants	62.8 Years STANDARD_DEVIATION 12.8 • n=5 Participants	63.8 Years STANDARD_DEVIATION 11.6 • n=4 Participants
Sex: Female, Male Female	315 Participants n=5 Participants	26 Participants n=7 Participants	156 Participants n=5 Participants	497 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	312 Participants n=5 Participants	24 Participants n=7 Participants	151 Participants n=5 Participants	487 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants

PRIMARY outcome

Timeframe: At 24 weeks after last patient enrolled in trial

Population: Full Analysis Set. Please note that the statistical significance test (test comparing groups) i.e., statistical analysis was not applicable for this outcome measure, since the primary objective was to assess the rate (per cohort) and not to compare two or more treatment arms, as this was a non-randomized, single arm open label trial.

Outcome measures

Outcome measures
Measure	Ribociclib + Letrozole Cohort A n=307 Participants postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.	Ribociclib + Letrozole Cohort B1 n=26 Participants premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B2 n=154 Participants premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Total n=487 Participants Cohort A and Cohort B combined
Clinical Benefit Rate (CBR) in Women and Men With Hormone Receptor Positiv, HER-2 Negative Breast Cancer Treated With Ribocilib and Letrozole CBR by week 24 (= BOR of CR or PR or SD or NCRNPD(Confirmed Best Overall Response (BOR))	63.2 Percentage of Participants Interval 57.5 to 68.6	57.7 Percentage of Participants Interval 36.9 to 76.6	56.5 Percentage of Participants Interval 48.3 to 64.5	60.8 Percentage of Participants Interval 56.3 to 65.1
Clinical Benefit Rate (CBR) in Women and Men With Hormone Receptor Positiv, HER-2 Negative Breast Cancer Treated With Ribocilib and Letrozole CBR by week 24 (= BOR of CR or PR or SD or NCRNPD (non-confirmed BOR)	71.7 Percentage of Participants Interval 66.3 to 76.6	69.2 Percentage of Participants Interval 48.2 to 85.7	64.3 Percentage of Participants Interval 56.2 to 71.8	69.2 Percentage of Participants Interval 64.9 to 73.3

SECONDARY outcome

Timeframe: At week 24 , week 48 and week 72

Population: Full Analysis Set

PFS based on radiologic assessment by investigator using RECIST 1.1 criteria

Outcome measures

Outcome measures
Measure	Ribociclib + Letrozole Cohort A n=307 Participants postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.	Ribociclib + Letrozole Cohort B1 n=26 Participants premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B2 n=154 Participants premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Total Cohort A and Cohort B combined
Progression Free Survival (PFS) for Different Populations - Kaplan-Meier Estimates (%, 95% CI) Kaplan-Meier estimates (%, 95% CI) - Week 24	73.1 Percentage of Participants Interval 67.3 to 77.9	67.0 Percentage of Participants Interval 44.7 to 82.0	63.8 Percentage of Participants Interval 55.2 to 71.3	—
Progression Free Survival (PFS) for Different Populations - Kaplan-Meier Estimates (%, 95% CI) Kaplan-Meier estimates (%, 95% CI) - Week 48	61.9 Percentage of Participants Interval 55.7 to 67.5	58.7 Percentage of Participants Interval 36.8 to 75.2	47.5 Percentage of Participants Interval 38.7 to 55.7	—
Progression Free Survival (PFS) for Different Populations - Kaplan-Meier Estimates (%, 95% CI) Kaplan-Meier estimates (%, 95% CI) - week 72	54.5 Percentage of Participants Interval 48.1 to 60.5	49.6 Percentage of Participants Interval 28.6 to 67.6	39.3 Percentage of Participants Interval 30.8 to 47.6	—

SECONDARY outcome

Timeframe: Up to approximately month 25

Population: Full Analysis Set

PFS based on radiologic assessment by investigator using RECIST 1.1 criteria

Outcome measures

Outcome measures
Measure	Ribociclib + Letrozole Cohort A n=307 Participants postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.	Ribociclib + Letrozole Cohort B1 n=26 Participants premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B2 n=154 Participants premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Total Cohort A and Cohort B combined
Progression Free Survival (PFS) for Different Populations - Median Time to Progression or Death With 95% CI [Months]	21.8 Months Interval 13.9 to 25.3	16.5 Months Interval 3.2 to The upper limit was not estimable. Existence of the confidence limits does not directly depend on the Kaplan-Meier curve itself (dropping below 0.75, 0.5 or 0.25), but on the curves that represent the confidence limits (CL) for the survivor function. They envelop the Kaplan-Meier curve.	8.8 Months Interval 8.1 to 16.3	—

SECONDARY outcome

Timeframe: At Week 24, Week 48 and Week 72

Population: Full Analysis Set

Overall survival (OS) defined as the time from date of start of treatment to date of death due to any cause. For the Kaplan-Meier estimates (%, 95% CI), the probability of survival at week 24, 48 and 72 is reported below.

Outcome measures

Outcome measures
Measure	Ribociclib + Letrozole Cohort A n=307 Participants postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.	Ribociclib + Letrozole Cohort B1 n=26 Participants premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B2 n=154 Participants premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Total Cohort A and Cohort B combined
Overall Survival (OS) - Kaplan-Meier Estimates (%, 95% CI) Kaplan-Meier estimates (%, 95% CI) - Week 24	98.6 Percentage of Participants Interval 96.4 to 99.5	100.0 Percentage of Participants Interval 100.0 to 100.0	93.9 Percentage of Participants Interval 88.5 to 96.8	—
Overall Survival (OS) - Kaplan-Meier Estimates (%, 95% CI) Kaplan-Meier estimates (%, 95% CI) - Week 48	93.3 Percentage of Participants Interval 89.7 to 95.7	87.5 Percentage of Participants Interval 66.1 to 95.8	86.1 Percentage of Participants Interval 79.2 to 90.8	—
Overall Survival (OS) - Kaplan-Meier Estimates (%, 95% CI) Kaplan-Meier estimates (%, 95% CI) - Week 72	89.7 Percentage of Participants Interval 85.5 to 92.7	87.5 Percentage of Participants Interval 66.1 to 95.8	81.0 Percentage of Participants Interval 73.5 to 86.6	—

SECONDARY outcome

Timeframe: Up to approximatley 38 months

Population: Full Analysis Set

Overall survival (OS) defined as the time from date of start of treatment to date of death due to any cause.

Outcome measures

Outcome measures
Measure	Ribociclib + Letrozole Cohort A n=307 Participants postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.	Ribociclib + Letrozole Cohort B1 n=26 Participants premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B2 n=154 Participants premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Total Cohort A and Cohort B combined
Overall Survival (OS) - Median Time to Progression or Death With 95% CI [Months]	NA Months Not estimable. Existence of the confidence limits does not directly depend on the Kaplan-Meier curve itself (dropping below 0.75, 0.5 or 0.25), but on the curves that represent the confidence limits (CL) for the survivor function. They envelop the Kaplan-Meier curve.	NA Months Interval 30.9 to Not estimable. Existence of the confidence limits does not directly depend on the Kaplan-Meier curve itself (dropping below 0.75, 0.5 or 0.25), but on the curves that represent the confidence limits (CL) for the survivor function. They envelop the Kaplan-Meier curve.	NA Months Interval 31.0 to Not estimable. Existence of the confidence limits does not directly depend on the Kaplan-Meier curve itself (dropping below 0.75, 0.5 or 0.25), but on the curves that represent the confidence limits (CL) for the survivor function. They envelop the Kaplan-Meier curve.	—

SECONDARY outcome

Timeframe: Up to approximatley 38 months

Population: Full Analysis Set

Overall survival (OS) defined as the time from date of start of treatment to date of death due to any cause.

Outcome measures

Outcome measures
Measure	Ribociclib + Letrozole Cohort A n=307 Participants postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.	Ribociclib + Letrozole Cohort B1 n=26 Participants premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B2 n=154 Participants premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Total Cohort A and Cohort B combined
Overall Survival (OS) - Number of Censored Participants and Number of Deaths No. of censored (no death), n	240 Participants	17 Participants	94 Participants	—
Overall Survival (OS) - Number of Censored Participants and Number of Deaths No. of events (deaths due to any cause), n	67 Participants	9 Participants	60 Participants	—

SECONDARY outcome

Timeframe: At week 24

Population: Full Analysis Set

Overall response rate (ORR) is the best overall response (BOR) of complete response (CR) or partial response (PR) as defined by RECIST 1.1.

Outcome measures

Outcome measures
Measure	Ribociclib + Letrozole Cohort A n=307 Participants postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.	Ribociclib + Letrozole Cohort B1 n=26 Participants premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B2 n=154 Participants premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Total Cohort A and Cohort B combined
Overall Response Rate (ORR) - Kaplan-Meier Estimates (%, 95% CI) ORR by week 24 - (BOR of CR or PR) (confirmed)	22.8 Percentage of Participants Interval 18.2 to 27.9	23.1 Percentage of Participants Interval 9.0 to 43.6	11.7 Percentage of Participants Interval 7.1 to 17.8	—
Overall Response Rate (ORR) - Kaplan-Meier Estimates (%, 95% CI) ORR by week 24 - (BOR of CR or PR) (unconfirmed)	24.8 Percentage of Participants Interval 20.0 to 30.0	30.8 Percentage of Participants Interval 14.3 to 51.8	16.2 Percentage of Participants Interval 10.8 to 23.0	—

SECONDARY outcome

Timeframe: Change from Baseline to Week 24

Population: Full Analysis Set. Included in the analysis are all patients with valid assessment at baseline and week 24. Some questions were conditional branching and thus did not apply to some participants. Also, some participants chose not to answer some questions / items; the responses were accepted as provided by the participants. Also, some participants discontinued during the course of the trial, and thus less measurements were taken at week 24 than at baseline.

The QLQ-C30 is the core questionnaire of the EORTC QLQ, which has been developed for the assessment of the health-related QOL of cancer patients participating in international clinical trials. Using a linear transformation to standardize the raw scores, all scores finally range from 0 to 100, where a higher score represents a higher response level, e.g., a higher ("better") level of functioning (applies to the first 6 items, items 1 to 6), but a higher ("worse") level of symptoms (applies to the last 9 items, items 7 to 15). There is no aggregated total score, i.e., all scale scores were analyzed separately.

Outcome measures

SECONDARY outcome

Timeframe: Baseline and Week 24 (Cycle 7)

To evaluate health related quality of life (QoL) via EORTC BR-23. The scoring approach for the QLQ-BR23 is identical in principle to that for the function and symptom scales / single items of the QLQ-C30, i.e., all scores finally range from 0 to 100, where a higher score represents a higher response level, e.g., a higher ("better") level of functioning, (applies to the first 4 items, items 1 to 4) but a higher ("worse") level of symptoms (applies to the last 4 items, items 5 to 8).

Outcome measures

Outcome measures
Measure	Ribociclib + Letrozole Cohort A n=307 Participants postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.	Ribociclib + Letrozole Cohort B1 n=26 Participants premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B2 n=154 Participants premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Total n=180 Participants Cohort A and Cohort B combined
Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) EORTC QLQ-BR23 SEXUAL FUNCTIONING during the study - change from baseline at cycle 7	-1.1 Scores on a scale Standard Deviation 17.7	0.0 Scores on a scale Standard Deviation 24.5	0.8 Scores on a scale Standard Deviation 18.0	0.7 Scores on a scale Standard Deviation 19.1
Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) EORTC QLQ-BR23 SYSTEMATIC THERAPY during the study - change from baseline at cycle 7	-9.4 Scores on a scale Standard Deviation 16.6	-13 Scores on a scale Standard Deviation 22.3	-6.0 Scores on a scale Standard Deviation 14.9	-7.1 Scores on a scale Standard Deviation 16.4
Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) EORTC QLQ-BR23 HAIR LOSS during the study - change from baseline at cycle 7	-22 Scores on a scale Standard Deviation 43.4	-17 Scores on a scale Standard Deviation 23.6	-14 Scores on a scale Standard Deviation 33.9	-15 Scores on a scale Standard Deviation 32.1
Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) EORTC QLQ-BR23 BODY IMAGE during the study - change from baseline at cycle 7	-1.5 Scores on a scale Standard Deviation 18.2	-0.6 Scores on a scale Standard Deviation 22.2	0.4 Scores on a scale Standard Deviation 22.7	0.2 Scores on a scale Standard Deviation 22.5
Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) EORTC QLQ-BR23 SEXUAL ENJOYMENT during the study - change from baseline at cycle 7	-1.9 Scores on a scale Standard Deviation 31.3	-17 Scores on a scale Standard Deviation 23.6	7.4 Scores on a scale Standard Deviation 26.9	5.0 Scores on a scale Standard Deviation 27.1
Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) EORTC QLQ-BR23 FUTURE PERSPECTIVE during the study - change from baseline at cycle 7	-20 Scores on a scale Standard Deviation 33.4	-24 Scores on a scale Standard Deviation 26.6	-12 Scores on a scale Standard Deviation 26.2	-14 Scores on a scale Standard Deviation 26.5
Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) EORTC QLQ-BR23 BREAST SYMPTOMS during the study - change from baseline at cycle 7	3.3 Scores on a scale Standard Deviation 15.7	8.3 Scores on a scale Standard Deviation 22.7	0.9 Scores on a scale Standard Deviation 17.5	2.2 Scores on a scale Standard Deviation 18.6
Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) EORTC QLQ-BR23 ARM SYMPTOMS during the study - change from baseline at cycle 7	4.1 Scores on a scale Standard Deviation 21.1	-1.5 Scores on a scale Standard Deviation 22.6	-2.1 Scores on a scale Standard Deviation 18.1	-2.0 Scores on a scale Standard Deviation 18.8

SECONDARY outcome

Timeframe: up to approximately 10 months

Population: Full Analysis Set

Time to 10% deterioration in the European Organisation for Research and Treatment of Cancer (EORTC) global health status

Outcome measures

Outcome measures
Measure	Ribociclib + Letrozole Cohort A n=307 Participants postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.	Ribociclib + Letrozole Cohort B1 n=26 Participants premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B2 n=154 Participants premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Total n=487 Participants Cohort A and Cohort B combined
Time to 10% Deterioration in EORTC Global Health Status	3.3 months Interval 2.8 to 4.6	3.7 months Interval 1.8 to 10.1	2.8 months Interval 1.8 to 4.6	3.0 months Interval 2.8 to 4.6

SECONDARY outcome

Timeframe: Up to Week 72

Population: Safety Set

Adverse Events (AEs) were separated into TEAEs (defined as AEs occurring/worsening from first study drug treatment until 30 days after the last study drug treatment) and AEs in the pre-/post-treatment period.

Outcome measures

Outcome measures
Measure	Ribociclib + Letrozole Cohort A n=319 Participants postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.	Ribociclib + Letrozole Cohort B1 n=26 Participants premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B2 n=157 Participants premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Total Cohort A and Cohort B combined
Number of Participants With Treatment Emergent Adverse Events (TEAE) Total AEs (i.e., Includes any type of AE.)	318 Number of Participants	25 Number of Participants	157 Number of Participants	—
Number of Participants With Treatment Emergent Adverse Events (TEAE) Serious AEs	97 Number of Participants	5 Number of Participants	45 Number of Participants	—
Number of Participants With Treatment Emergent Adverse Events (TEAE) Non-serious AEs	317 Number of Participants	25 Number of Participants	157 Number of Participants	—
Number of Participants With Treatment Emergent Adverse Events (TEAE) AEs with suspected relationship to ribociclib	302 Number of Participants	25 Number of Participants	144 Number of Participants	—
Number of Participants With Treatment Emergent Adverse Events (TEAE) AEs leading to discontinuation of ribociclib	76 Number of Participants	7 Number of Participants	38 Number of Participants	—
Number of Participants With Treatment Emergent Adverse Events (TEAE) AEs with fatal outcome	6 Number of Participants	0 Number of Participants	6 Number of Participants	—

POST_HOC outcome

Timeframe: on-treatment deaths: up to approx 3.15 years; all deaths: approx 3.15 years

Population: Clinical database population - all treated participants

On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 1150 days (approx 3.15 years). (Treatment duration ranged from 2 days to 1120 days). Deaths post treatment survival follow up were collected after the on- treatment period, up to approx. 3.15 years. Patients who didn't die during the on-treatment period and had not stopped study participation at the time of data cut-off (end of study) were censored.

Outcome measures

Outcome measures
Measure	Ribociclib + Letrozole Cohort A n=319 Participants postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.	Ribociclib + Letrozole Cohort B1 n=26 Participants premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B2 n=157 Participants premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Total n=502 Participants Cohort A and Cohort B combined
All Collected Deaths on-treatment deaths	6 Participants	0 Participants	6 Participants	12 Participants
All Collected Deaths Total deaths	67 Participants	9 Participants	60 Participants	136 Participants

Adverse Events

Ribociclib + Letrozole Cohort A

Serious events: 97 serious events

Other events: 315 other events

Deaths: 6 deaths

Ribociclib + Letrozole Cohort B

Serious events: 50 serious events

Other events: 181 other events

Deaths: 6 deaths

Ribociclib + Letrozole Cohort B1

Serious events: 5 serious events

Other events: 25 other events

Deaths: 0 deaths

Ribociclib + Letrozole Cohort B2

Serious events: 45 serious events

Other events: 156 other events

Deaths: 6 deaths

Total

Serious events: 147 serious events

Other events: 496 other events

Deaths: 12 deaths

Serious adverse events

Serious adverse events
Measure	Ribociclib + Letrozole Cohort A n=319 participants at risk postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.	Ribociclib + Letrozole Cohort B n=183 participants at risk premenopausal women or perimenopausal women or postmenopausal women, or men; naïve + pre-treated All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o.daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B1 n=26 participants at risk premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B2 n=157 participants at risk premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Total n=502 participants at risk Total
Gastrointestinal disorders VOMITING	0.94% 3/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.60% 3/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
General disorders CHEST PAIN	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Blood and lymphatic system disorders ANAEMIA	1.3% 4/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.2% 4/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.5% 4/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.6% 8/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Blood and lymphatic system disorders DISSEMINATED INTRAVASCULAR COAGULATION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Blood and lymphatic system disorders FEBRILE NEUTROPENIA	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.6% 3/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 1/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.3% 2/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.60% 3/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Blood and lymphatic system disorders HYPERFIBRINOLYSIS	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Blood and lymphatic system disorders LEUKOPENIA	0.63% 2/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Blood and lymphatic system disorders NEUTROPENIA	0.63% 2/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.1% 2/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.3% 2/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.80% 4/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Blood and lymphatic system disorders PANCYTOPENIA	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Blood and lymphatic system disorders THROMBOCYTOPENIA	0.94% 3/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.60% 3/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Cardiac disorders ATRIAL FIBRILLATION	0.63% 2/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.1% 2/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.3% 2/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.80% 4/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Cardiac disorders BRADYARRHYTHMIA	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Cardiac disorders CARDIAC ARREST	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Cardiac disorders CARDIAC FAILURE	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Cardiac disorders MYOCARDIAL INFARCTION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Cardiac disorders SUPRAVENTRICULAR TACHYCARDIA	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Endocrine disorders HYPERTHYROIDISM	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders ABDOMINAL PAIN	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders ABDOMINAL PAIN LOWER	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders ANAL HAEMORRHAGE	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders CONSTIPATION	0.63% 2/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders DIARRHOEA	0.94% 3/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.80% 4/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders GASTRITIS	0.94% 3/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.60% 3/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders GASTROOESOPHAGEAL REFLUX DISEASE	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders ILEUS	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders INTESTINAL STRANGULATION	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders NAUSEA	2.2% 7/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.1% 2/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.3% 2/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.8% 9/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
General disorders COMPLICATION OF DEVICE INSERTION	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
General disorders DEATH	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
General disorders FATIGUE	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.1% 2/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.3% 2/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
General disorders GENERAL PHYSICAL HEALTH DETERIORATION	0.63% 2/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.7% 5/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.2% 5/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.4% 7/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
General disorders IMPAIRED HEALING	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.1% 2/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.3% 2/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.60% 3/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
General disorders OEDEMA PERIPHERAL	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
General disorders PAIN	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
General disorders PYREXIA	1.9% 6/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.4% 7/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Hepatobiliary disorders BILE DUCT STENOSIS	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Hepatobiliary disorders BILIARY COLIC	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Hepatobiliary disorders CHOLECYSTITIS	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Hepatobiliary disorders CHOLECYSTITIS ACUTE	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Hepatobiliary disorders CHOLELITHIASIS	0.63% 2/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Hepatobiliary disorders DRUG-INDUCED LIVER INJURY	1.6% 5/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.2% 6/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Hepatobiliary disorders HEPATIC CIRRHOSIS	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Hepatobiliary disorders HEPATOTOXICITY	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Hepatobiliary disorders JAUNDICE	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations ABDOMINAL ABSCESS	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations ABSCESS JAW	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations APPENDICITIS	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations ATYPICAL PNEUMONIA	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations BRONCHITIS	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations CHOLECYSTITIS INFECTIVE	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations CYSTITIS	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations CYSTITIS ESCHERICHIA	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations DEVICE RELATED INFECTION	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.1% 2/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.3% 2/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations DIVERTICULITIS	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations EMPHYSEMATOUS CHOLECYSTITIS	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations ERYSIPELAS	0.94% 3/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.60% 3/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations ESCHERICHIA INFECTION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations FEBRILE INFECTION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations GASTROENTERITIS	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations GASTROINTESTINAL INFECTION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations HELICOBACTER GASTRITIS	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations INFECTIOUS PLEURAL EFFUSION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations INFLUENZA	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations MASTITIS	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations PNEUMONIA	2.5% 8/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.1% 2/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.3% 2/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.0% 10/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations PROTEUS INFECTION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations PYELONEPHRITIS	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations RESPIRATORY SYNCYTIAL VIRUS INFECTION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations SEPSIS	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations URINARY TRACT INFECTION	0.94% 3/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.60% 3/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations UROSEPSIS	0.63% 2/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications ACCIDENT	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications ANKLE FRACTURE	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 1/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications CERVICAL VERTEBRAL FRACTURE	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications FALL	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications FEMORAL NECK FRACTURE	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications FEMUR FRACTURE	0.94% 3/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.60% 3/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications HIP FRACTURE	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications HUMERUS FRACTURE	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications INCISIONAL HERNIA	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications JAW FRACTURE	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications POST PROCEDURAL HAEMORRHAGE	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 1/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications POST-TRAUMATIC PAIN	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications POSTOPERATIVE ADHESION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications PROCEDURAL COMPLICATION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications RADIUS FRACTURE	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications RIB FRACTURE	0.94% 3/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.60% 3/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications TIBIA FRACTURE	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications UPPER LIMB FRACTURE	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations ALANINE AMINOTRANSFERASE INCREASED	1.6% 5/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.2% 6/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	0.94% 3/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.80% 4/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations BLOOD BILIRUBIN INCREASED	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations C-REACTIVE PROTEIN INCREASED	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations HAEMOGLOBIN DECREASED	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations NEUTROPHIL COUNT DECREASED	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 1/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations WHITE BLOOD CELL COUNT DECREASED	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 1/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Metabolism and nutrition disorders DECREASED APPETITE	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Metabolism and nutrition disorders DEHYDRATION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Metabolism and nutrition disorders HYPERCALCAEMIA	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Metabolism and nutrition disorders HYPERKALAEMIA	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Metabolism and nutrition disorders HYPONATRAEMIA	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Metabolism and nutrition disorders HYPOPHAGIA	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Metabolism and nutrition disorders TUMOUR LYSIS SYNDROME	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders ARTHRALGIA	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders BACK PAIN	0.63% 2/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders BONE LESION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders BONE PAIN	0.63% 2/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.1% 2/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.3% 2/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.80% 4/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders FLANK PAIN	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders LUMBAR SPINAL STENOSIS	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders MOBILITY DECREASED	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL CHEST PAIN	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders OSTEITIS	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders OSTEOARTHRITIS	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders OSTEONECROSIS OF JAW	0.63% 2/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	0.63% 2/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders SPINAL PAIN	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BRONCHIAL CARCINOMA	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) CANCER PAIN	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) COLON CANCER	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) MALIGNANT PLEURAL EFFUSION	0.63% 2/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) METASTASES TO BONE	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) METASTASES TO SPINE	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) RENAL CELL CARCINOMA	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SQUAMOUS CELL CARCINOMA OF THE TONGUE	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 1/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) TUMOUR PAIN	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Nervous system disorders CEREBRAL ISCHAEMIA	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Nervous system disorders CEREBROVASCULAR ACCIDENT	0.63% 2/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Nervous system disorders DIZZINESS	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Nervous system disorders HEADACHE	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Nervous system disorders MONOPLEGIA	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Nervous system disorders NEUROPATHY PERIPHERAL	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Nervous system disorders PARAESTHESIA	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Nervous system disorders PERIPHERAL NERVE LESION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Nervous system disorders SYNCOPE	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Product Issues DEVICE LOOSENING	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Psychiatric disorders DEPRESSION	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Psychiatric disorders PANIC ATTACK	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Psychiatric disorders SOMATIC SYMPTOM DISORDER	0.63% 2/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Renal and urinary disorders ACUTE KIDNEY INJURY	1.6% 5/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 1/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.2% 6/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Renal and urinary disorders HAEMATURIA	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Renal and urinary disorders KIDNEY CONGESTION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Renal and urinary disorders RENAL DISORDER	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Renal and urinary disorders RENAL FAILURE	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Renal and urinary disorders RENAL IMPAIRMENT	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Renal and urinary disorders URETERIC STENOSIS	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Renal and urinary disorders URETEROLITHIASIS	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Renal and urinary disorders URINARY INCONTINENCE	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Renal and urinary disorders URINARY RETENTION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Renal and urinary disorders URINARY TRACT OBSTRUCTION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Reproductive system and breast disorders PELVIC PAIN	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Respiratory, thoracic and mediastinal disorders ASTHMA	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	2.8% 9/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.6% 3/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.9% 3/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.4% 12/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Respiratory, thoracic and mediastinal disorders DYSPNOEA EXERTIONAL	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Respiratory, thoracic and mediastinal disorders HYPERVENTILATION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	0.94% 3/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.6% 3/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.9% 3/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.2% 6/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Respiratory, thoracic and mediastinal disorders PNEUMONITIS	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Respiratory, thoracic and mediastinal disorders PNEUMOTHORAX	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	2.2% 7/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.6% 8/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Respiratory, thoracic and mediastinal disorders PULMONARY FIBROSIS	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Respiratory, thoracic and mediastinal disorders RESPIRATORY FAILURE	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Skin and subcutaneous tissue disorders SKIN ULCER	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Vascular disorders CIRCULATORY COLLAPSE	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Vascular disorders HYPERTENSION	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Vascular disorders HYPERTENSIVE CRISIS	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Vascular disorders HYPOTENSION	0.31% 1/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.20% 1/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.

Other adverse events

Other adverse events
Measure	Ribociclib + Letrozole Cohort A n=319 participants at risk postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.	Ribociclib + Letrozole Cohort B n=183 participants at risk premenopausal women or perimenopausal women or postmenopausal women, or men; naïve + pre-treated All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o.daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B1 n=26 participants at risk premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B2 n=157 participants at risk premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Total n=502 participants at risk Total
Blood and lymphatic system disorders ANAEMIA	14.4% 46/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	19.7% 36/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	26.9% 7/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	18.5% 29/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	16.3% 82/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Blood and lymphatic system disorders LEUKOPENIA	23.8% 76/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	21.3% 39/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	30.8% 8/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	19.7% 31/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	22.9% 115/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Blood and lymphatic system disorders LYMPHOPENIA	2.2% 7/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.1% 2/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.8% 9/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Blood and lymphatic system disorders NEUTROPENIA	50.8% 162/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	48.1% 88/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	57.7% 15/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	46.5% 73/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	49.8% 250/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Blood and lymphatic system disorders THROMBOCYTOPENIA	8.2% 26/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	9.8% 18/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 1/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	10.8% 17/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	8.8% 44/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Ear and labyrinth disorders VERTIGO	10.3% 33/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	9.3% 17/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	15.4% 4/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	8.3% 13/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	10.0% 50/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Eye disorders DRY EYE	7.2% 23/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	5.5% 10/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	5.1% 8/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	6.6% 33/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Eye disorders LACRIMATION INCREASED	10.7% 34/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	6.0% 11/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	5.7% 9/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	9.0% 45/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders ABDOMINAL PAIN	4.7% 15/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 14/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	19.2% 5/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	5.7% 9/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	5.8% 29/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders ABDOMINAL PAIN UPPER	10.3% 33/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.1% 13/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	11.5% 3/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	6.4% 10/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	9.2% 46/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders CONSTIPATION	19.4% 62/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	17.5% 32/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	15.4% 4/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	17.8% 28/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	18.7% 94/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders DIARRHOEA	26.6% 85/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	21.9% 40/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	30.8% 8/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	20.4% 32/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	24.9% 125/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders DRY MOUTH	8.8% 28/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	5.5% 10/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 1/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	5.7% 9/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.6% 38/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders DYSPEPSIA	7.8% 25/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 14/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.6% 12/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.8% 39/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders NAUSEA	40.8% 130/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	42.1% 77/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	34.6% 9/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	43.3% 68/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	41.2% 207/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders STOMATITIS	10.3% 33/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	14.8% 27/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	15.4% 4/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	14.6% 23/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	12.0% 60/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders TOOTHACHE	2.8% 9/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.2% 4/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.3% 2/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.6% 13/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Gastrointestinal disorders VOMITING	20.7% 66/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	16.9% 31/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	19.2% 5/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	16.6% 26/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	19.3% 97/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
General disorders FATIGUE	38.6% 123/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	40.4% 74/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	57.7% 15/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	37.6% 59/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	39.2% 197/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
General disorders OEDEMA PERIPHERAL	11.0% 35/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	12.0% 22/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	19.2% 5/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	10.8% 17/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	11.4% 57/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
General disorders PYREXIA	7.2% 23/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 14/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	15.4% 4/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	6.4% 10/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.4% 37/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Immune system disorders SEASONAL ALLERGY	1.3% 4/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.3% 6/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	11.5% 3/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.9% 3/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.0% 10/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations BRONCHITIS	6.0% 19/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.7% 5/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 1/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.5% 4/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	4.8% 24/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations CYSTITIS	6.6% 21/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	4.9% 9/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	11.5% 3/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 6/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	6.0% 30/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations GASTROINTESTINAL INFECTION	0.63% 2/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.6% 3/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.00% 5/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations NASOPHARYNGITIS	29.5% 94/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	26.8% 49/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	38.5% 10/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	24.8% 39/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	28.5% 143/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Infections and infestations URINARY TRACT INFECTION	9.7% 31/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	9.3% 17/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 1/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	10.2% 16/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	9.6% 48/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications ARTHROPOD BITE	0.94% 3/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.6% 3/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.2% 6/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Injury, poisoning and procedural complications ARTHROPOD STING	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.1% 2/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations ALANINE AMINOTRANSFERASE INCREASED	23.5% 75/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	19.7% 36/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	23.1% 6/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	19.1% 30/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	22.1% 111/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	20.7% 66/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	19.7% 36/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	19.2% 5/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	19.7% 31/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	20.3% 102/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations BLOOD BILIRUBIN INCREASED	5.0% 16/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.55% 1/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.64% 1/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.4% 17/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations BLOOD CREATININE INCREASED	8.5% 27/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	6.6% 12/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	6.4% 10/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.8% 39/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations BLOOD LACTATE DEHYDROGENASE INCREASED	5.3% 17/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.6% 3/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 1/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.3% 2/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	4.0% 20/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations BLOOD THYROID STIMULATING HORMONE INCREASED	0.00% 0/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.1% 2/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.40% 2/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations ELECTROCARDIOGRAM QT PROLONGED	7.2% 23/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 14/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 1/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	8.3% 13/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.4% 37/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations GAMMA-GLUTAMYLTRANSFERASE INCREASED	10.3% 33/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	9.8% 18/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	19.2% 5/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	8.3% 13/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	10.2% 51/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations NEUTROPHIL COUNT DECREASED	12.5% 40/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	13.7% 25/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	14.6% 23/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	12.9% 65/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations WEIGHT DECREASED	5.0% 16/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	4.9% 9/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	5.7% 9/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	5.0% 25/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations WEIGHT INCREASED	2.2% 7/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.2% 4/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.3% 2/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.2% 11/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Investigations WHITE BLOOD CELL COUNT DECREASED	8.5% 27/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	9.8% 18/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	10.2% 16/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	9.0% 45/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Metabolism and nutrition disorders DECREASED APPETITE	13.8% 44/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	10.4% 19/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 1/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	11.5% 18/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	12.5% 63/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Metabolism and nutrition disorders HYPERKALAEMIA	1.9% 6/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.2% 4/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.3% 2/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.0% 10/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Metabolism and nutrition disorders HYPOCALCAEMIA	2.5% 8/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.7% 5/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.9% 3/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.6% 13/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders ARTHRALGIA	17.9% 57/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	21.3% 39/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	34.6% 9/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	19.1% 30/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	19.1% 96/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders BACK PAIN	11.6% 37/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	13.1% 24/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	15.4% 4/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	12.7% 20/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	12.2% 61/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders BONE PAIN	11.0% 35/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	8.2% 15/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	23.1% 6/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	5.7% 9/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	10.0% 50/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL CHEST PAIN	3.8% 12/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.3% 6/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.5% 4/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.6% 18/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	6.6% 21/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 14/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.6% 12/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.0% 35/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders MYALGIA	5.6% 18/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.3% 6/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 6/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	4.8% 24/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	16.3% 52/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	12.6% 23/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	11.5% 3/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	12.7% 20/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	14.9% 75/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Nervous system disorders DIZZINESS	8.2% 26/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	6.6% 12/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	15.4% 4/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	5.1% 8/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.6% 38/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Nervous system disorders DYSGEUSIA	6.3% 20/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	6.0% 11/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	15.4% 4/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	4.5% 7/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	6.2% 31/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Nervous system disorders HEADACHE	17.6% 56/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	19.7% 36/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	38.5% 10/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	16.6% 26/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	18.3% 92/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Nervous system disorders HYPOAESTHESIA	0.94% 3/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.7% 5/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	11.5% 3/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.3% 2/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.6% 8/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Nervous system disorders POLYNEUROPATHY	5.0% 16/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.7% 5/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 1/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	2.5% 4/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	4.2% 21/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Psychiatric disorders DEPRESSION	2.2% 7/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	4.4% 8/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 6/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.0% 15/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Psychiatric disorders INSOMNIA	9.7% 31/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	14.2% 26/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	15.4% 4/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	14.0% 22/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	11.4% 57/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Psychiatric disorders SLEEP DISORDER	4.1% 13/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	5.5% 10/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	15.4% 4/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 6/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	4.6% 23/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Reproductive system and breast disorders VULVOVAGINAL DRYNESS	1.3% 4/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.6% 3/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	11.5% 3/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	0.00% 0/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.4% 7/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Respiratory, thoracic and mediastinal disorders COUGH	16.6% 53/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	12.0% 22/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	23.1% 6/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	10.2% 16/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	14.9% 75/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	15.4% 49/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	13.7% 25/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	15.4% 4/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	13.4% 21/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	14.7% 74/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	3.4% 11/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 7/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	19.2% 5/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	1.3% 2/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.6% 18/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Skin and subcutaneous tissue disorders ALOPECIA	37.3% 119/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	31.1% 57/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	19.2% 5/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	33.1% 52/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	35.1% 176/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Skin and subcutaneous tissue disorders DRY SKIN	7.5% 24/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	8.2% 15/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	11.5% 3/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.6% 12/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.8% 39/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Skin and subcutaneous tissue disorders ERYTHEMA	2.8% 9/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	5.5% 10/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 1/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	5.7% 9/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	3.8% 19/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Skin and subcutaneous tissue disorders PRURITUS	14.1% 45/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	9.8% 18/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	11.5% 3/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	9.6% 15/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	12.5% 63/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Skin and subcutaneous tissue disorders RASH	14.7% 47/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	10.4% 19/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	7.7% 2/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	10.8% 17/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	13.1% 66/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Vascular disorders HOT FLUSH	13.8% 44/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	16.4% 30/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	42.3% 11/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	12.1% 19/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	14.7% 74/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.
Vascular disorders HYPERTENSION	11.3% 36/319 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	6.0% 11/183 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	15.4% 4/26 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	4.5% 7/157 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.	9.4% 47/502 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of 1150 days (approx. 3.15 years).(Treatment duration ranged from 2 days to 1120 days.) For this study, disease progression was NOT classified as an Adverse Event.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Ribociclib + Letrozole Cohort A n=307 Participants postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.	Ribociclib + Letrozole Cohort B1 n=26 Participants premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Ribociclib + Letrozole Cohort B2 n=154 Participants premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly	Total n=180 Participants Cohort A and Cohort B combined
Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 Global health status - Change from baseline to Week 24 (C7D1)	8.8 Scores on a scale Standard Deviation 23.7	11.7 Scores on a scale Standard Deviation 20.8	5.0 Scores on a scale Standard Deviation 26.2	6.1 Scores on a scale Standard Deviation 25.4
Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 Physical Functioning - Change from baseline to Week 24 (C7D1)	-3.1 Scores on a scale Standard Deviation 19.9	-3.6 Scores on a scale Standard Deviation 10.7	-2.2 Scores on a scale Standard Deviation 17.7	-2.4 Scores on a scale Standard Deviation 16.7
Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 Role Functioning - Change from baseline to Week 24 (C7D1)	-6.6 Scores on a scale Standard Deviation 31.9	-17 Scores on a scale Standard Deviation 21.8	-1.3 Scores on a scale Standard Deviation 34.7	-3.9 Scores on a scale Standard Deviation 33.3
Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 Emotional Functioning - Change from baseline to Week 24 (C7D1)	-9.6 Scores on a scale Standard Deviation 24.2	-9.4 Scores on a scale Standard Deviation 25.0	-3.6 Scores on a scale Standard Deviation 21.8	-4.6 Scores on a scale Standard Deviation 22.4
Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 Cognitive Functioning - Change from baseline to Week 24 (C7D1)	2.7 Scores on a scale Standard Deviation 23.7	2.2 Scores on a scale Standard Deviation 28.1	1.1 Scores on a scale Standard Deviation 21.6	1.3 Scores on a scale Standard Deviation 22.7
Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 Nausea / Vomiting - Change from baseline to Week 24 (C7D1)	0.1 Scores on a scale Standard Deviation 16.7	1.1 Scores on a scale Standard Deviation 22.2	-4.9 Scores on a scale Standard Deviation 19.1	-3.9 Scores on a scale Standard Deviation 19.7
Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 Pain - Change from baseline to Week 24 (C7D1)	13.2 Scores on a scale Standard Deviation 31.9	15.6 Scores on a scale Standard Deviation 24.8	9.0 Scores on a scale Standard Deviation 27.6	10.1 Scores on a scale Standard Deviation 27.1
Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 Insomnia - Change from baseline to Week 24 (C7D1)	4.2 Scores on a scale Standard Deviation 33.2	6.7 Scores on a scale Standard Deviation 31.4	4.9 Scores on a scale Standard Deviation 32.7	5.2 Scores on a scale Standard Deviation 32.3
Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 Appetite loss - Change from baseline to Week 24 (C7D1)	11.2 Scores on a scale Standard Deviation 33.7	6.7 Scores on a scale Standard Deviation 28.7	1.4 Scores on a scale Standard Deviation 30.9	2.2 Scores on a scale Standard Deviation 30.5
Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 Constipation - Change from baseline to Week 24 (C7D1)	-2.7 Scores on a scale Standard Deviation 26.6	2.2 Scores on a scale Standard Deviation 26.6	-3.6 Scores on a scale Standard Deviation 27.9	-2.6 Scores on a scale Standard Deviation 27.6
Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 Diarrhea - Change from baseline to Week 24 (C7D1)	2.6 Scores on a scale Standard Deviation 24.6	0.0 Scores on a scale Standard Deviation 45.4	2.3 Scores on a scale Standard Deviation 27.2	1.9 Scores on a scale Standard Deviation 30.7
Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 Financial Problems - Change from baseline to Week 24 (C7D1)	0.2 Scores on a scale Standard Deviation 27.7	-4.4 Scores on a scale Standard Deviation 24.8	-1.4 Scores on a scale Standard Deviation 25.1	-1.9 Scores on a scale Standard Deviation 24.9
Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 Social Functioning - Change from baseline to Week 24 (C7D1)	-6.9 Scores on a scale Standard Deviation 27.9	-16 Scores on a scale Standard Deviation 21.3	-5.3 Scores on a scale Standard Deviation 31.3	-7.0 Scores on a scale Standard Deviation 30.0
Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 Fatigue - Change from baseline to Week 24 (C7D1)	6.3 Scores on a scale Standard Deviation 25.9	11.1 Scores on a scale Standard Deviation 20.6	3.9 Scores on a scale Standard Deviation 27.1	5.1 Scores on a scale Standard Deviation 26.1
Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 Dyspnoea - Change from baseline to Week 24 (C7D1)	3.8 Scores on a scale Standard Deviation 32.4	4.4 Scores on a scale Standard Deviation 21.3	-5.3 Scores on a scale Standard Deviation 30.5	-3.7 Scores on a scale Standard Deviation 29.3