Trial Outcomes & Findings for An Open Label Study of Postmenopausal Women With Oestrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Treated With Everolimus (RAD001) With Exemestane, With Exploratory Epigenetic Marker Analysis (NCT NCT01743560)

NCT ID: NCT01743560

Last Updated: 2019-07-18

Results Overview

The best Overall Response (OR) for each patient is determined from the sequence of investigator overall lesion responses according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1.). To be assigned a best OR of Complete Responese (CR) at least two determinations of CR at least 4 weeks apart before progression are required. To be assigned a best OR of Partial Response (PR) at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) are required.The Overall Response Rate (ORR) was defined as the proportion of patients with a best OR of confirmed CR or PR by week 48.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 52 participants
• Primary outcome timeframe: At 48 weeks
• Results posted on: 2019-07-18

Participant Flow

Sixty-seven patients were screened and 52 patients were enrolled.

Participant milestones

Measure	Everolimus and Exemestane Postmenopausal women diagnosed with oestrogen receptor positive locally advanced or metastatic breast cancer will receive everolimus at a dose of 10mg daily p.o. and exemestane 25mg daily p.o.
Overall Study STARTED	52
Overall Study Full Analysis Set (FAS)	49
Overall Study Safety Analysis Set (SAF)	49
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	43

Reasons for withdrawal

Measure	Everolimus and Exemestane Postmenopausal women diagnosed with oestrogen receptor positive locally advanced or metastatic breast cancer will receive everolimus at a dose of 10mg daily p.o. and exemestane 25mg daily p.o.
Overall Study Disease progression	26
Overall Study Adverse Event	8
Overall Study Death	3
Overall Study Withdrawal by Subject	2
Overall Study Protocol Violation	1
Overall Study >1 dose of study drug	3

Baseline Characteristics

An Open Label Study of Postmenopausal Women With Oestrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Treated With Everolimus (RAD001) With Exemestane, With Exploratory Epigenetic Marker Analysis

Baseline characteristics by cohort

Measure	Everolimus and Exemestane n=49 Participants Postmenopausal women diagnosed with oestrogen receptor positive locally advanced or metastatic breast cancer will receive everolimus at a dose of 10mg daily p.o. and exemestane 25mg daily p.o.
Age, Continuous	61.3 years STANDARD_DEVIATION 8.71 • n=5 Participants
Sex: Female, Male Female	49 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	48 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants
Weight	71.1 kg STANDARD_DEVIATION 15.44 • n=5 Participants

PRIMARY outcome

Timeframe: At 48 weeks

Population: FAS

The best Overall Response (OR) for each patient is determined from the sequence of investigator overall lesion responses according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1.). To be assigned a best OR of Complete Responese (CR) at least two determinations of CR at least 4 weeks apart before progression are required. To be assigned a best OR of Partial Response (PR) at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) are required.The Overall Response Rate (ORR) was defined as the proportion of patients with a best OR of confirmed CR or PR by week 48.

Outcome measures

Measure	Everolimus and Exemestane n=49 Participants Postmenopausal women diagnosed with oestrogen receptor positive locally advanced or metastatic breast cancer will receive everolimus at a dose of 10mg daily p.o. and exemestane 25mg daily p.o.	Week 24 Change from baseline at Week 24	Week 36 Change from baseline at week 36	Week 48 Change from baseline at week 48	Week 48
Best Overall Response of Everolimus and Exemestane Treatment in Postmenopausal Women With Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer Patients with non-measurable disease at baseline	10 participants	—	—	—	—
Best Overall Response of Everolimus and Exemestane Treatment in Postmenopausal Women With Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer Best at WK 48 - Complete Response (CR)	0 participants	—	—	—	—
Best Overall Response of Everolimus and Exemestane Treatment in Postmenopausal Women With Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer Patients with measurable disease at baseline	39 participants	—	—	—	—
Best Overall Response of Everolimus and Exemestane Treatment in Postmenopausal Women With Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer Best at WK 48 - Partial Response (PR)	7 participants	—	—	—	—
Best Overall Response of Everolimus and Exemestane Treatment in Postmenopausal Women With Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer Best at WK 48 - Stable Disease (SD)	18 participants	—	—	—	—
Best Overall Response of Everolimus and Exemestane Treatment in Postmenopausal Women With Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer Best at WK 48 - Progressive Disease (PD)	15 participants	—	—	—	—
Best Overall Response of Everolimus and Exemestane Treatment in Postmenopausal Women With Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer Unknown	1 participants	—	—	—	—
Best Overall Response of Everolimus and Exemestane Treatment in Postmenopausal Women With Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer Missing	8 participants	—	—	—	—

PRIMARY outcome

Timeframe: At 48 weeks

Population: FAS

The Overall Response Rate (ORR) was defined as the proportion of patients with a best OR of confirmed CR or PR by week 48. Treatment success is defined as: The best Overall Response (OR) for each patient is determined from the sequence of investigator overall lesion responses according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1.). To be assigned a best OR of Complete Responese (CR) at least two determinations of CR at least 4 weeks apart before progression are required. To be assigned a best OR of Partial Response (PR) at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) are required.

Outcome measures

Measure	Everolimus and Exemestane n=49 Participants Postmenopausal women diagnosed with oestrogen receptor positive locally advanced or metastatic breast cancer will receive everolimus at a dose of 10mg daily p.o. and exemestane 25mg daily p.o.	Week 24 Change from baseline at Week 24	Week 36 Change from baseline at week 36	Week 48 Change from baseline at week 48	Week 48
Overall Response Rate of Everolimus and Exemestane Treatment in Postmenopausal Women With Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer	14.3 Percentage of participants Interval 6.0 to 27.0	—	—	—	—

SECONDARY outcome

Timeframe: Start of treatment to the date of event defined as first documented progression due to any cause up to approximately 48 weeks

Population: Full analysis set

Progression-free survival (PFS) is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Tumor assessment and response was evaluated according to RECIST v1.1Response was assessed by local radiology review.

Outcome measures

Measure	Everolimus and Exemestane n=49 Participants Postmenopausal women diagnosed with oestrogen receptor positive locally advanced or metastatic breast cancer will receive everolimus at a dose of 10mg daily p.o. and exemestane 25mg daily p.o.	Week 24 Change from baseline at Week 24	Week 36 Change from baseline at week 36	Week 48 Change from baseline at week 48	Week 48
Progression-free Survival (PFS) Events as Per Investigators - FAS Progression of disease	25 Number of events	—	—	—	—
Progression-free Survival (PFS) Events as Per Investigators - FAS Deaths	8 Number of events Interval 12.71 to 34.29	—	—	—	—
Progression-free Survival (PFS) Events as Per Investigators - FAS Number of censored observations	16 Number of events	—	—	—	—

SECONDARY outcome

Timeframe: Start of treatment to the date of event defined as first documented progression due to any cause up to approximately 48 weeks

Population: Full analysis set

Progression-free survival (PFS) is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Tumor assessment and response was evaluated according to RECIST v1.1Response was assessed by local radiology review.

Outcome measures

Measure	Everolimus and Exemestane n=49 Participants Postmenopausal women diagnosed with oestrogen receptor positive locally advanced or metastatic breast cancer will receive everolimus at a dose of 10mg daily p.o. and exemestane 25mg daily p.o.	Week 24 Change from baseline at Week 24	Week 36 Change from baseline at week 36	Week 48 Change from baseline at week 48	Week 48
Progression-free Survival (PFS) by Median Time in Weeks as Per Investigators - FAS	23.6 weeks Interval 12.71 to 34.29	—	—	—	—

SECONDARY outcome

Timeframe: Start of treatment to the date of event defined as first documented progression due to any cause up to approximately 48 weeks

Population: Full analysis set

Progression-free survival (PFS) is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Tumor assessment and response was evaluated according to RECIST v1.1Response was assessed by local radiology review. The PFS was analyzed using the Kaplan Meier method.

Outcome measures

Measure	Everolimus and Exemestane n=49 Participants Postmenopausal women diagnosed with oestrogen receptor positive locally advanced or metastatic breast cancer will receive everolimus at a dose of 10mg daily p.o. and exemestane 25mg daily p.o.	Week 24 Change from baseline at Week 24	Week 36 Change from baseline at week 36	Week 48 Change from baseline at week 48	Week 48
Progression-free Survival (PFS) - % Event-free Probability Estimate - FAS Event free at 12 weeks	67.9 Percentage of participants Interval 51.82 to 79.56	—	—	—	—
Progression-free Survival (PFS) - % Event-free Probability Estimate - FAS Event free at 24 weeks	49.1 Percentage of participants Interval 32.98 to 63.44	—	—	—	—
Progression-free Survival (PFS) - % Event-free Probability Estimate - FAS Event free at 36 weeks	28.9 Percentage of participants Interval 15.42 to 43.87	—	—	—	—
Progression-free Survival (PFS) - % Event-free Probability Estimate - FAS Event free at 48 weeks	18.4 Percentage of participants Interval 7.38 to 33.19	—	—	—	—

SECONDARY outcome

Timeframe: Start of treatment to the date of death up to approximately 48 weeks

Population: Full analysis set

Overall survival (OS) is defined as the time from date of start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last contact. Time to median OS was not estimable.

Outcome measures

Measure	Everolimus and Exemestane n=49 Participants Postmenopausal women diagnosed with oestrogen receptor positive locally advanced or metastatic breast cancer will receive everolimus at a dose of 10mg daily p.o. and exemestane 25mg daily p.o.	Week 24 Change from baseline at Week 24	Week 36 Change from baseline at week 36	Week 48 Change from baseline at week 48	Week 48
Overall Survival (OS) Events (Number of Deaths) - FAS Deaths	8 Number of events Interval 12.71 to 34.29	—	—	—	—
Overall Survival (OS) Events (Number of Deaths) - FAS Number of censored observations	41 Number of events	—	—	—	—

SECONDARY outcome

Timeframe: Start of treatment to the date of death up to approximately 48 weeks

Population: Full analysis set

Overall survival (OS) is defined as the time from date of start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last contact.

Outcome measures

Measure	Everolimus and Exemestane n=49 Participants Postmenopausal women diagnosed with oestrogen receptor positive locally advanced or metastatic breast cancer will receive everolimus at a dose of 10mg daily p.o. and exemestane 25mg daily p.o.	Week 24 Change from baseline at Week 24	Week 36 Change from baseline at week 36	Week 48 Change from baseline at week 48	Week 48
Overall Survival (OS) - % Event-free Probability Estimate - FAS Event free at 24 weeks	83.9 Percentage of participants Interval 66.92 to 92.6	—	—	—	—
Overall Survival (OS) - % Event-free Probability Estimate - FAS Event free at 36 weeks	74.2 Percentage of participants Interval 53.02 to 86.88	—	—	—	—
Overall Survival (OS) - % Event-free Probability Estimate - FAS Event free at 12 weeks	93.3 Percentage of participants Interval 80.57 to 97.78	—	—	—	—
Overall Survival (OS) - % Event-free Probability Estimate - FAS Event free at 48 weeks	74.2 Percentage of participants Interval 53.02 to 86.88	—	—	—	—

SECONDARY outcome

Timeframe: Baseline 12,24,36,48 weeks

Population: number of participants varied across visits

The QLQ-C30 is composed of multi-item scales and single-item measures including 5 functional scales, 3 symptom scales, a global health status-QoL scale, and 6 single items. Each of the multi-item scales includes a different set of items - no item occurs in more than 1 scale. High scale score=higher response level; a high score for a functional scale=a healthy level of function, high score for the global health status/QoL=high quality of life but a high score for a symptom scale / item=high level of symptomatology/problems. The principle for scoring these scales: 1.) Estimate the average of the items that contribute to the scale = raw score. 2.) Linear transformation to standardize the raw score, so that scores range from 0 to 100. Results should be interpreted with caution as the numbers of patients with available data over time were limited, and because of high variances as evidenced by large standard deviations

Outcome measures

Measure	Everolimus and Exemestane n=27 Participants Postmenopausal women diagnosed with oestrogen receptor positive locally advanced or metastatic breast cancer will receive everolimus at a dose of 10mg daily p.o. and exemestane 25mg daily p.o.	Week 24 n=17 Participants Change from baseline at Week 24	Week 36 n=13 Participants Change from baseline at week 36	Week 48 n=28 Participants Change from baseline at week 48	Week 48
Change From Baseline EORTC Quality of Life Questionnaire of Cancer Patients QLQ-C30 at Each Time Point Global health status/QoL	-9.0 scores Standard Deviation 22.04	-3.6 scores Standard Deviation 19.71	1.9 scores Standard Deviation 16.37	-8.3 scores Standard Deviation 22.48	—
Change From Baseline EORTC Quality of Life Questionnaire of Cancer Patients QLQ-C30 at Each Time Point Role functioning	-4.5 scores Standard Deviation 33.19	3.1 scores Standard Deviation 23.74	8.3 scores Standard Deviation 23.03	-12.3 scores Standard Deviation 30.52	—
Change From Baseline EORTC Quality of Life Questionnaire of Cancer Patients QLQ-C30 at Each Time Point Social functioning	-9.9 scores Standard Deviation 25.00	-9.4 scores Standard Deviation 24.32	3.8 scores Standard Deviation 15.45	-14.7 scores Standard Deviation 31.74	—
Change From Baseline EORTC Quality of Life Questionnaire of Cancer Patients QLQ-C30 at Each Time Point Physical functioning	-5.1 scores Standard Deviation 19.16	-1.0 scores Standard Deviation 14.52	4.9 scores Standard Deviation 13.79	-10.8 scores Standard Deviation 29.97	—
Change From Baseline EORTC Quality of Life Questionnaire of Cancer Patients QLQ-C30 at Each Time Point Emotional functioning	2.6 scores Standard Deviation 21.36	-3.1 scores Standard Deviation 14.87	7.5 scores Standard Deviation 9.90	0.6 scores Standard Deviation 21.59	—
Change From Baseline EORTC Quality of Life Questionnaire of Cancer Patients QLQ-C30 at Each Time Point Cognitive functioning	-8.6 scores Standard Deviation 21.37	-5.2 scores Standard Deviation 17.97	1.3 scores Standard Deviation 22.01	-3.7 scores Standard Deviation 21.35	—
Change From Baseline EORTC Quality of Life Questionnaire of Cancer Patients QLQ-C30 at Each Time Point Fatigue	8.6 scores Standard Deviation 26.92	9.5 scores Standard Deviation 15.93	0.9 scores Standard Deviation 16.64	7.3 scores Standard Deviation 24.66	—
Change From Baseline EORTC Quality of Life Questionnaire of Cancer Patients QLQ-C30 at Each Time Point Nausea/ vomiting	-1.2 scores Standard Deviation 15.96	2.9 scores Standard Deviation 16.91	-3.8 scores Standard Deviation 15.45	-2.4 scores Standard Deviation 23.88	—
Change From Baseline EORTC Quality of Life Questionnaire of Cancer Patients QLQ-C30 at Each Time Point Pain	1.2 scores Standard Deviation 26.12	3.9 scores Standard Deviation 24.67	-1.3 scores Standard Deviation 20.93	0.6 scores Standard Deviation 24.64	—
Change From Baseline EORTC Quality of Life Questionnaire of Cancer Patients QLQ-C30 at Each Time Point Dyspnea	18.5 scores Standard Deviation 37.36	8.3 scores Standard Deviation 25.82	2.6 scores Standard Deviation 25.32	10.7 scores Standard Deviation 27.30	—
Change From Baseline EORTC Quality of Life Questionnaire of Cancer Patients QLQ-C30 at Each Time Point Insomnia	3.7 scores Standard Deviation 26.69	2.0 scores Standard Deviation 29.98	0 scores Standard Deviation 23.57	-3.6 scores Standard Deviation 37.78	—
Change From Baseline EORTC Quality of Life Questionnaire of Cancer Patients QLQ-C30 at Each Time Point Appetite loss	30.9 scores Standard Deviation 40.22	23.5 scores Standard Deviation 28.30	12.8 scores Standard Deviation 28.99	16.7 scores Standard Deviation 35.72	—
Change From Baseline EORTC Quality of Life Questionnaire of Cancer Patients QLQ-C30 at Each Time Point Constipation	4.9 scores Standard Deviation 32.95	11.8 scores Standard Deviation 28.73	10.3 scores Standard Deviation 21.01	8.3 scores Standard Deviation 19.51	—
Change From Baseline EORTC Quality of Life Questionnaire of Cancer Patients QLQ-C30 at Each Time Point Diarrhea	4.9 scores Standard Deviation 25.66	8.3 scores Standard Deviation 37.52	-5.1 scores Standard Deviation 22.96	7.4 scores Standard Deviation 28.24	—
Change From Baseline EORTC Quality of Life Questionnaire of Cancer Patients QLQ-C30 at Each Time Point Financial problems	-1.2 scores Standard Deviation 21.64	-10.4 scores Standard Deviation 26.44	-10.3 scores Standard Deviation 21.01	-2.6 scores Standard Deviation 18.67	—

SECONDARY outcome

Timeframe: Baseline 12,24,36,48 weeks

EuroQoL Quality of Life Scale (EQ-5D) is a standardized instrument to assess health state values is a standardized instrument to assess health state values. The EQ-5D essentially consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (VAS). The EQ-5D descriptive system is comprised of the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. Percentage of participants' responses were presented by visits. Results should be interpreted with caution as the numbers of patients with available data over time were limited.

Outcome measures

Measure	Everolimus and Exemestane n=49 Participants Postmenopausal women diagnosed with oestrogen receptor positive locally advanced or metastatic breast cancer will receive everolimus at a dose of 10mg daily p.o. and exemestane 25mg daily p.o.	Week 24 n=49 Participants Change from baseline at Week 24	Week 36 n=49 Participants Change from baseline at week 36	Week 48 n=49 Participants Change from baseline at week 48	Week 48 n=49 Participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Usual activities - slight problems	22.4 Percentage of participants	16.3 Percentage of participants	2.0 Percentage of participants	8.2 Percentage of participants	14.3 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Pain/discomfort - severe	4.1 Percentage of participants	4.1 Percentage of participants	0 Percentage of participants	0 Percentage of participants	4.1 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Anxiety/depression - moderate	16.3 Percentage of participants	12.2 Percentage of participants	6.1 Percentage of participants	0 Percentage of participants	8.2 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Mobility-severe problem	6.1 Percentage of participants	2.0 Percentage of participants	0 Percentage of participants	2.0 Percentage of participants	6.1 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Mobility-unable to walk	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	4.1 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Self-care - no problem	69.4 Percentage of participants	44.9 Percentage of participants	34.7 Percentage of participants	24.5 Percentage of participants	40.8 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Self-care - slight problem	18.4 Percentage of participants	4.1 Percentage of participants	0 Percentage of participants	0 Percentage of participants	10.2 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Self-care - moderate problem	6.1 Percentage of participants	8.2 Percentage of participants	2.0 Percentage of participants	2.0 Percentage of participants	4.1 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Self-care -severe problem	2.0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	2.0 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Self-care - unable	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Usual activities - no problems	30.6 Percentage of participants	14.3 Percentage of participants	22.4 Percentage of participants	14.3 Percentage of participants	18.4 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Usual activities - moderate problems	28.6 Percentage of participants	22.4 Percentage of participants	12.2 Percentage of participants	2.0 Percentage of participants	12.2 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Usual activities - severe problems	10.2 Percentage of participants	4.1 Percentage of participants	0 Percentage of participants	2.0 Percentage of participants	6.1 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Usual activities -unable to do	4.1 Percentage of participants	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	6.1 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Pain/discomfort - none	20.4 Percentage of participants	14.3 Percentage of participants	10.2 Percentage of participants	12.2 Percentage of participants	18.4 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Pain/discomfort - slight	30.6 Percentage of participants	16.3 Percentage of participants	18.4 Percentage of participants	8.2 Percentage of participants	20.4 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Pain/discomfort - moderate	40.8 Percentage of participants	22.4 Percentage of participants	8.2 Percentage of participants	6.1 Percentage of participants	14.3 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Pain/discomfort - extreme	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Anxiety/depression - none	44.9 Percentage of participants	22.4 Percentage of participants	18.4 Percentage of participants	16.3 Percentage of participants	22.4 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Anxiety/depression - slight	34.7 Percentage of participants	22.4 Percentage of participants	12.2 Percentage of participants	10.2 Percentage of participants	20.4 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Anxiety/depression - severe	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	6.1 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Anxiety/depression - extreme	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Mobility-no problem	38.8 Percentage of participants	20.4 Percentage of participants	18.4 Percentage of participants	14.3 Percentage of participants	16.3 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Mobility-slight problem	18.4 Percentage of participants	14.3 Percentage of participants	10.2 Percentage of participants	8.2 Percentage of participants	16.3 Percentage of participants
Percentage of Patient Responses in EuroQoL 5-dimension Questionnaire - FAS Mobility-moderate problem	32.7 Percentage of participants	20.4 Percentage of participants	8.2 Percentage of participants	2.0 Percentage of participants	14.3 Percentage of participants

SECONDARY outcome

Timeframe: Baseline 12,24,36,48 weeks

EuroQoL Quality of Life Scale (EQ-5D) is a standardized instrument to assess health state values. The EQ-5D essentially consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (VAS). For the visual analogue scale, participants draw a line from a box to the point on the thermometer-like scale corresponding to their health state, 0-100 (100 = Best health state). Weights are used to score the responses to the 5 domains, with scores ranging from 0 to 1 (where a score of 1 represents a perfect state). Scores for the visual analogue scale reflect the position where participant's line crosses the thermometer-like scale. Results should be interpreted with caution as the numbers of patients with available data over time were limited, and because of high variances as evidenced by large standard deviations

Outcome measures

Measure	Everolimus and Exemestane n=25 Participants Postmenopausal women diagnosed with oestrogen receptor positive locally advanced or metastatic breast cancer will receive everolimus at a dose of 10mg daily p.o. and exemestane 25mg daily p.o.	Week 24 n=16 Participants Change from baseline at Week 24	Week 36 n=12 Participants Change from baseline at week 36	Week 48 n=27 Participants Change from baseline at week 48	Week 48
Change From Baseline in EuroQoL 5-dimension Visual Analogue Scores - FAS	-7.9 units on a scale Standard Deviation 18.98	-6.1 units on a scale Standard Deviation 12.47	-6.3 units on a scale Standard Deviation 10.03	-11.6 units on a scale Standard Deviation 22.58	—

Adverse Events

Everolimus + Exemestane

Serious events: 22 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Measure	Everolimus + Exemestane n=49 participants at risk Everolimus + Exemestane
Blood and lymphatic system disorders Anaemia	4.1% 2/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Pericardial effusion	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Tachycardia	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Abdominal pain	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Abdominal pain upper	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Colitis	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Duodenal ulcer	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Gastric ulcer	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Haematemesis	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Oral pain	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Vomiting	4.1% 2/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Mucosal inflammation	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Infections and infestations Lower respiratory tract infection	8.2% 4/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Infections and infestations Pneumonia	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Infections and infestations Urinary tract infection	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Injury, poisoning and procedural complications Fall	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Injury, poisoning and procedural complications Overdose	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Dehydration	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Hypercalcaemia	4.1% 2/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Hyperglycaemia	4.1% 2/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Hyperkalaemia	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Hypoglycaemia	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Musculoskeletal and connective tissue disorders Arthralgia	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Musculoskeletal and connective tissue disorders Muscular weakness	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Musculoskeletal and connective tissue disorders Pain in extremity	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Nervous system disorders Hemiparesis	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Nervous system disorders Lethargy	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Nervous system disorders Neuropathy peripheral	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Nervous system disorders Seizure	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Nervous system disorders Somnolence	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Nervous system disorders Spinal cord compression	4.1% 2/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Psychiatric disorders Confusional state	6.1% 3/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Renal and urinary disorders Renal failure	4.1% 2/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Respiratory, thoracic and mediastinal disorders Non-cardiogenic pulmonary oedema	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Respiratory, thoracic and mediastinal disorders Pneumonitis	4.1% 2/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.0% 1/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.

Other adverse events

Measure	Everolimus + Exemestane n=49 participants at risk Everolimus + Exemestane
Blood and lymphatic system disorders Anaemia	16.3% 8/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Thrombocytopenia	8.2% 4/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Abdominal distension	6.1% 3/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Abdominal pain	10.2% 5/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Constipation	16.3% 8/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Diarrhoea	44.9% 22/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Dry mouth	8.2% 4/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Dyspepsia	10.2% 5/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Mouth ulceration	22.4% 11/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Nausea	28.6% 14/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Oral pain	12.2% 6/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Stomatitis	14.3% 7/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Vomiting	16.3% 8/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Axillary pain	8.2% 4/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Fatigue	44.9% 22/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Mucosal inflammation	34.7% 17/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Oedema peripheral	6.1% 3/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Peripheral swelling	6.1% 3/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Infections and infestations Lower respiratory tract infection	8.2% 4/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Infections and infestations Oral candidiasis	10.2% 5/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Infections and infestations Urinary tract infection	12.2% 6/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Investigations Alanine aminotransferase increased	8.2% 4/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Investigations Aspartate aminotransferase increased	8.2% 4/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Investigations Blood cholesterol increased	6.1% 3/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Investigations Blood creatinine increased	8.2% 4/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Investigations Gamma-glutamyltransferase increased	12.2% 6/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Investigations Weight decreased	12.2% 6/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Decreased appetite	32.7% 16/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Hypercalcaemia	8.2% 4/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Hyperglycaemia	6.1% 3/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Musculoskeletal and connective tissue disorders Arthralgia	6.1% 3/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Musculoskeletal and connective tissue disorders Back pain	12.2% 6/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Musculoskeletal and connective tissue disorders Joint swelling	6.1% 3/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	10.2% 5/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Musculoskeletal and connective tissue disorders Pain in extremity	14.3% 7/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Nervous system disorders Dysgeusia	14.3% 7/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Nervous system disorders Headache	6.1% 3/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Psychiatric disorders Depressed mood	8.2% 4/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Psychiatric disorders Insomnia	8.2% 4/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Respiratory, thoracic and mediastinal disorders Cough	36.7% 18/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Respiratory, thoracic and mediastinal disorders Dyspnoea	22.4% 11/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Respiratory, thoracic and mediastinal disorders Epistaxis	16.3% 8/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.1% 3/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Respiratory, thoracic and mediastinal disorders Pneumonitis	6.1% 3/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Respiratory, thoracic and mediastinal disorders Productive cough	6.1% 3/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Skin and subcutaneous tissue disorders Pruritus	12.2% 6/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Skin and subcutaneous tissue disorders Rash	36.7% 18/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Vascular disorders Lymphoedema	6.1% 3/49 • Adverse Events (AEs) are collected from the First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. Consistent with EudracCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: Novartis.email@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. 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 (ie, data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER