Trial Outcomes & Findings for Phase II Trial of Continuation Therapy in Advanced NSCLC (NCT NCT03083808)

NCT ID: NCT03083808

Last Updated: 2023-08-24

Results Overview

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter(LD) of target lesions; Progressive Disease (PD): \>= 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. PFS was defined as time from starting treatment to disease progression met by RECIST 1.1, start of additional anticancer therapy before progression, or death from any cause.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 35 participants
• Primary outcome timeframe: Time of treatment start until the criteria for disease progression or death, up to a maximum of 28 months
• Results posted on: 2023-08-24

Participant Flow

Participant milestones

Measure	Pembrolizumab 200mg IV Every 21 Days Patients who have been treated with a PD-1 or PD-L1 inhibitor and experienced a PFS of ≥3 months will be enrolled within 6 weeks of last dose of PD-1 or PD-L1 inhibitor. On Day 1 of each 3-week cycle, subjects will first receive pembrolizumab at a dose of 200mg IV every three weeks in combination with chemotherapy. Partner chemotherapy will be either gemcitabine 1000mg/m\^2 IV D1 and D8 every three weeks, docetaxel 75mg/m\^2 IV D1 every three weeks, or pemetrexed 500mg/m\^2 IV D1 every 3 weeks (pemetrexed for non-squamous histologies only). Subjects will continue to receive this combination until progression or intolerable toxicity. Pembrolizumab: Pembrolizumab 200mg IV every 21 days \+ Physician's choice chemotherapy with one of the following every 21 days: * Docetaxel 75mg/m2 IV * Pemetrexed 500mg/m2 IV (non-squamous only) * Gemcitabine 1000mg/m2 IV on days 1 and 8
Overall Study STARTED	35
Overall Study COMPLETED	35
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase II Trial of Continuation Therapy in Advanced NSCLC

Baseline characteristics by cohort

Measure	Pembrolizumab 200mg IV Every 21 Days n=35 Participants Patients who have been treated with a PD-1 or PD-L1 inhibitor and experienced a PFS of ≥3 months will be enrolled within 6 weeks of last dose of PD-1 or PD-L1 inhibitor. On Day 1 of each 3-week cycle, subjects will first receive pembrolizumab at a dose of 200mg IV every three weeks in combination with chemotherapy. Partner chemotherapy will be either gemcitabine 1000mg/m\^2 IV D1 and D8 every three weeks, docetaxel 75mg/m\^2 IV D1 every three weeks, or pemetrexed 500mg/m\^2 IV D1 every 3 weeks (pemetrexed for non-squamous histologies only). Subjects will continue to receive this combination until progression or intolerable toxicity. Pembrolizumab: Pembrolizumab 200mg IV every 21 days \+ Physician's choice chemotherapy with one of the following every 21 days: * Docetaxel 75mg/m2 IV * Pemetrexed 500mg/m2 IV (non-squamous only) * Gemcitabine 1000mg/m2 IV on days 1 and 8
Age, Continuous	63 years n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants
Race (NIH/OMB) White	26 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	35 participants n=5 Participants
Histology Adenocarcinoma	26 Participants n=5 Participants
Histology Squamous cell carcinoma	7 Participants n=5 Participants
Histology Non-small cell, not otherwise specified	2 Participants n=5 Participants
Smoking Status Current	3 Participants n=5 Participants
Smoking Status Former	26 Participants n=5 Participants
Smoking Status Never	6 Participants n=5 Participants
Baseline ECOG ECOG = 1	26 Participants n=5 Participants
Baseline ECOG ECOG = 0	9 Participants n=5 Participants
Prior checkpoints inhibitors (CPI) Pembrolizumab	21 Participants n=5 Participants
Prior checkpoints inhibitors (CPI) Nivolumab	7 Participants n=5 Participants
Prior checkpoints inhibitors (CPI) Atezolizumab	5 Participants n=5 Participants
Prior checkpoints inhibitors (CPI) Durvalumab	1 Participants n=5 Participants
Prior checkpoints inhibitors (CPI) Spartalizumab	1 Participants n=5 Participants
First-line Chemo Carboplatin + Pemetrexed	21 Participants n=5 Participants
First-line Chemo Carboplatin + Taxane	12 Participants n=5 Participants
First-line Chemo Cisplatin based chemo	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Time of treatment start until the criteria for disease progression or death, up to a maximum of 28 months

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter(LD) of target lesions; Progressive Disease (PD): >= 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

PFS was defined as time from starting treatment to disease progression met by RECIST 1.1, start of additional anticancer therapy before progression, or death from any cause.

Outcome measures

Measure

Pembrolizumab 200mg IV Every 21 Days n=35 Participants Patients who have been treated with a PD-1 or PD-L1 inhibitor and experienced a PFS of ≥3 months will be enrolled within 6 weeks of last dose of PD-1 or PD-L1 inhibitor. On Day 1 of each 3-week cycle, subjects will first receive pembrolizumab at a dose of 200mg IV every three weeks in combination with chemotherapy. Partner chemotherapy will be either gemcitabine 1000mg/m\^2 IV D1 and D8 every three weeks, docetaxel 75mg/m\^2 IV D1 every three weeks, or pemetrexed 500mg/m\^2 IV D1 every 3 weeks (pemetrexed for non-squamous histologies only). Subjects will continue to receive this combination until progression or intolerable toxicity. Pembrolizumab: Pembrolizumab 200mg IV every 21 days \+ Physician's choice chemotherapy with one of the following every 21 days: * Docetaxel 75mg/m2 IV * Pemetrexed 500mg/m2 IV (non-squamous only) * Gemcitabine 1000mg/m2 IV on days 1 and 8

Progression Free Survival (PFS)

5.1 months Interval 3.6 to 8.0

SECONDARY outcome

Timeframe: Up to a maximum of 28 months

Population: Out of 35 patients in the study, one subject was not evaluable for best response using RECIST 1.1 and two subjects were not evaluable for best response using irRECIST.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter(LD) of target lesions; Progressive Disease (PD) >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD.

Per Immune-Related RECIST (irRECIST): Complete Response(irCR), Disappearance of all measurable and non-measurable lesions; Partial Response (irPR) >=30% decrease in tumor burden relative to baseline; Progressive Disease (irPD), >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions confirmed by a consecutive assessment at least 4 week after first documentation; Stable Disease (irSD), not meeting criteria for irCR or irPR, in absence of irPD CBR is defined as any subject with SD for ≥ 3 months, PR or CR assessed via RECIST 1.1 and irRECIST.

Outcome measures

Measure	Pembrolizumab 200mg IV Every 21 Days n=34 Participants Patients who have been treated with a PD-1 or PD-L1 inhibitor and experienced a PFS of ≥3 months will be enrolled within 6 weeks of last dose of PD-1 or PD-L1 inhibitor. On Day 1 of each 3-week cycle, subjects will first receive pembrolizumab at a dose of 200mg IV every three weeks in combination with chemotherapy. Partner chemotherapy will be either gemcitabine 1000mg/m\^2 IV D1 and D8 every three weeks, docetaxel 75mg/m\^2 IV D1 every three weeks, or pemetrexed 500mg/m\^2 IV D1 every 3 weeks (pemetrexed for non-squamous histologies only). Subjects will continue to receive this combination until progression or intolerable toxicity. Pembrolizumab: Pembrolizumab 200mg IV every 21 days \+ Physician's choice chemotherapy with one of the following every 21 days: * Docetaxel 75mg/m2 IV * Pemetrexed 500mg/m2 IV (non-squamous only) * Gemcitabine 1000mg/m2 IV on days 1 and 8
Clinical Benefit Rate (CBR) CBR by RECIST1.1	24 Participants
Clinical Benefit Rate (CBR) CBR by irRECIST	24 Participants

SECONDARY outcome

Timeframe: Up to a maximum of 28 months

Population: Out of 35 patients, one subject was not evaluable for best response using RECIST 1.1 and two subjects were not evaluable for best response using irRECIST.

Per RECIST: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter(LD) of target lesions; Progressive Disease (PD) >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD.

Per irRECIST: Complete Response(irCR), Disappearance of all measurable and non-measurable lesions; Partial Response (irPR) >=30% decrease in tumor burden relative to baseline; Progressive Disease (irPD), >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions confirmed by a consecutive assessment at least 4 week after first documentation; Stable Disease (irSD), not meeting criteria for irCR or irPR, in absence of irPD ORR is defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1 and irRECIST, from the start of treatment until disease progression/recurrence

Outcome measures

Measure	Pembrolizumab 200mg IV Every 21 Days n=34 Participants Patients who have been treated with a PD-1 or PD-L1 inhibitor and experienced a PFS of ≥3 months will be enrolled within 6 weeks of last dose of PD-1 or PD-L1 inhibitor. On Day 1 of each 3-week cycle, subjects will first receive pembrolizumab at a dose of 200mg IV every three weeks in combination with chemotherapy. Partner chemotherapy will be either gemcitabine 1000mg/m\^2 IV D1 and D8 every three weeks, docetaxel 75mg/m\^2 IV D1 every three weeks, or pemetrexed 500mg/m\^2 IV D1 every 3 weeks (pemetrexed for non-squamous histologies only). Subjects will continue to receive this combination until progression or intolerable toxicity. Pembrolizumab: Pembrolizumab 200mg IV every 21 days \+ Physician's choice chemotherapy with one of the following every 21 days: * Docetaxel 75mg/m2 IV * Pemetrexed 500mg/m2 IV (non-squamous only) * Gemcitabine 1000mg/m2 IV on days 1 and 8
Objective Response Rate (ORR) ORR by RECIST1.1	23.5 percentage of participants Interval 10.8 to 41.2
Objective Response Rate (ORR) ORR by irRECIST	27.3 percentage of participants Interval 13.3 to 45.5

SECONDARY outcome

Timeframe: Time of treatment start until death or up to a maximum of 40 months

Time from date of treatment start to date of death from any cause

Outcome measures

Measure

Pembrolizumab 200mg IV Every 21 Days n=35 Participants Patients who have been treated with a PD-1 or PD-L1 inhibitor and experienced a PFS of ≥3 months will be enrolled within 6 weeks of last dose of PD-1 or PD-L1 inhibitor. On Day 1 of each 3-week cycle, subjects will first receive pembrolizumab at a dose of 200mg IV every three weeks in combination with chemotherapy. Partner chemotherapy will be either gemcitabine 1000mg/m\^2 IV D1 and D8 every three weeks, docetaxel 75mg/m\^2 IV D1 every three weeks, or pemetrexed 500mg/m\^2 IV D1 every 3 weeks (pemetrexed for non-squamous histologies only). Subjects will continue to receive this combination until progression or intolerable toxicity. Pembrolizumab: Pembrolizumab 200mg IV every 21 days \+ Physician's choice chemotherapy with one of the following every 21 days: * Docetaxel 75mg/m2 IV * Pemetrexed 500mg/m2 IV (non-squamous only) * Gemcitabine 1000mg/m2 IV on days 1 and 8

Overall Survival (OS)

24.5 months Interval 15.6 to 30.9

SECONDARY outcome

Timeframe: Adverse events were recorded from time of registration until 30 days after discontinuation of study drug(s) up to a maximum of 25 months.

Toxicity will be graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4

Outcome measures

Measure

Pembrolizumab 200mg IV Every 21 Days n=35 Participants Patients who have been treated with a PD-1 or PD-L1 inhibitor and experienced a PFS of ≥3 months will be enrolled within 6 weeks of last dose of PD-1 or PD-L1 inhibitor. On Day 1 of each 3-week cycle, subjects will first receive pembrolizumab at a dose of 200mg IV every three weeks in combination with chemotherapy. Partner chemotherapy will be either gemcitabine 1000mg/m\^2 IV D1 and D8 every three weeks, docetaxel 75mg/m\^2 IV D1 every three weeks, or pemetrexed 500mg/m\^2 IV D1 every 3 weeks (pemetrexed for non-squamous histologies only). Subjects will continue to receive this combination until progression or intolerable toxicity. Pembrolizumab: Pembrolizumab 200mg IV every 21 days \+ Physician's choice chemotherapy with one of the following every 21 days: * Docetaxel 75mg/m2 IV * Pemetrexed 500mg/m2 IV (non-squamous only) * Gemcitabine 1000mg/m2 IV on days 1 and 8

Number of Participants With Adverse Events

35 Participants

SECONDARY outcome

Timeframe: Time of treatment start until the criteria for disease progression or death, up to a maximum of 28 months

Per Immune-Related RECIST (irRECIST): Complete Response(irCR), Disappearance of all measurable and non-measurable lesions; Partial Reponse (irPR): >=30% decrease in in tumor burden relative to baseline; Progressive Disease (irPD), >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions confirmed by a consecutive assessment at least 4 week after first documentation; Stable Disease (irSD), not meeting criteria for irCR or irPR, in absence of irPD.

PFS is defined as time from the date of treatment start until the criteria for disease progression is met as defined by irRECIST or death occurs.

Outcome measures

Measure

Pembrolizumab 200mg IV Every 21 Days n=35 Participants Patients who have been treated with a PD-1 or PD-L1 inhibitor and experienced a PFS of ≥3 months will be enrolled within 6 weeks of last dose of PD-1 or PD-L1 inhibitor. On Day 1 of each 3-week cycle, subjects will first receive pembrolizumab at a dose of 200mg IV every three weeks in combination with chemotherapy. Partner chemotherapy will be either gemcitabine 1000mg/m\^2 IV D1 and D8 every three weeks, docetaxel 75mg/m\^2 IV D1 every three weeks, or pemetrexed 500mg/m\^2 IV D1 every 3 weeks (pemetrexed for non-squamous histologies only). Subjects will continue to receive this combination until progression or intolerable toxicity. Pembrolizumab: Pembrolizumab 200mg IV every 21 days \+ Physician's choice chemotherapy with one of the following every 21 days: * Docetaxel 75mg/m2 IV * Pemetrexed 500mg/m2 IV (non-squamous only) * Gemcitabine 1000mg/m2 IV on days 1 and 8

Progression Free Survival (PFS) by irRECIST

5.2 months Interval 3.6 to 9.8

Adverse Events

Pembrolizumab 200mg IV Every 21 Days

Serious events: 11 serious events

Other events: 34 other events

Deaths: 18 deaths

Serious adverse events

Measure	Pembrolizumab 200mg IV Every 21 Days n=35 participants at risk Patients who have been treated with a PD-1 or PD-L1 inhibitor and experienced a PFS of ≥3 months will be enrolled within 6 weeks of last dose of PD-1 or PD-L1 inhibitor. On Day 1 of each 3-week cycle, subjects will first receive pembrolizumab at a dose of 200mg IV every three weeks in combination with chemotherapy. Partner chemotherapy will be either gemcitabine 1000mg/m\^2 IV D1 and D8 every three weeks, docetaxel 75mg/m\^2 IV D1 every three weeks, or pemetrexed 500mg/m\^2 IV D1 every 3 weeks (pemetrexed for non-squamous histologies only). Subjects will continue to receive this combination until progression or intolerable toxicity. Pembrolizumab: Pembrolizumab 200mg IV every 21 days \+ Physician's choice chemotherapy with one of the following every 21 days: * Docetaxel 75mg/m2 IV * Pemetrexed 500mg/m2 IV (non-squamous only) * Gemcitabine 1000mg/m2 IV on days 1 and 8
Blood and lymphatic system disorders ANEMIA	5.7% 2/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders ASPIRATION	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Gastrointestinal disorders DIARRHEA	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders DYSPNEA	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
General disorders FEVER	5.7% 2/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Metabolism and nutrition disorders HYPERCALCEMIA	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Investigations NEUTROPHIL COUNT DECREASED	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Investigations PLATELET COUNT DECREASED	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Nervous system disorders SEIZURE	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Infections and infestations SEPSIS	5.7% 2/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Cardiac disorders SINUS BRADYCARDIA	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Vascular disorders THROMBOEMBOLIC EVENT	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) TUMOR PAIN	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.

Other adverse events

Measure	Pembrolizumab 200mg IV Every 21 Days n=35 participants at risk Patients who have been treated with a PD-1 or PD-L1 inhibitor and experienced a PFS of ≥3 months will be enrolled within 6 weeks of last dose of PD-1 or PD-L1 inhibitor. On Day 1 of each 3-week cycle, subjects will first receive pembrolizumab at a dose of 200mg IV every three weeks in combination with chemotherapy. Partner chemotherapy will be either gemcitabine 1000mg/m\^2 IV D1 and D8 every three weeks, docetaxel 75mg/m\^2 IV D1 every three weeks, or pemetrexed 500mg/m\^2 IV D1 every 3 weeks (pemetrexed for non-squamous histologies only). Subjects will continue to receive this combination until progression or intolerable toxicity. Pembrolizumab: Pembrolizumab 200mg IV every 21 days \+ Physician's choice chemotherapy with one of the following every 21 days: * Docetaxel 75mg/m2 IV * Pemetrexed 500mg/m2 IV (non-squamous only) * Gemcitabine 1000mg/m2 IV on days 1 and 8
Gastrointestinal disorders ABDOMINAL PAIN	8.6% 3/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Cardiac disorders ACUTE CORONARY SYNDROME	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Endocrine disorders ADRENAL INSUFFICIENCY	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Investigations ALANINE AMINOTRANSFERASE INCREASED	17.1% 6/35 • Number of events 15 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Immune system disorders ALLERGIC REACTION	5.7% 2/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders ALLERGIC RHINITIS	22.9% 8/35 • Number of events 10 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Skin and subcutaneous tissue disorders ALOPECIA	20.0% 7/35 • Number of events 9 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Nervous system disorders AMNESIA	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Blood and lymphatic system disorders ANEMIA	62.9% 22/35 • Number of events 86 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Metabolism and nutrition disorders ANOREXIA	40.0% 14/35 • Number of events 19 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Psychiatric disorders ANXIETY	37.1% 13/35 • Number of events 13 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Musculoskeletal and connective tissue disorders ARTHRALGIA	11.4% 4/35 • Number of events 6 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Musculoskeletal and connective tissue disorders ARTHRITIS	17.1% 6/35 • Number of events 6 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	22.9% 8/35 • Number of events 13 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders ASPIRATION	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Nervous system disorders ATAXIA	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Cardiac disorders ATRIAL FIBRILLATION	5.7% 2/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Musculoskeletal and connective tissue disorders BACK PAIN	28.6% 10/35 • Number of events 17 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Infections and infestations BLADDER INFECTION	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Blood and lymphatic system disorders BLOOD AND LYMPHATIC SYSTEM DISORDERS - OTHER, SPECIFY	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Investigations BLOOD BILIRUBIN INCREASED	8.6% 3/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Eye disorders BLURRED VISION	8.6% 3/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Musculoskeletal and connective tissue disorders BONE PAIN	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Reproductive system and breast disorders BREAST PAIN	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Infections and infestations BRONCHIAL INFECTION	2.9% 1/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders BRONCHOPULMONARY HEMORRHAGE	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Skin and subcutaneous tissue disorders BULLOUS DERMATITIS	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Injury, poisoning and procedural complications BURN	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Cardiac disorders CARDIAC DISORDERS - OTHER, SPECIFY	5.7% 2/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Investigations CD4 LYMPHOCYTES DECREASED	5.7% 2/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Cardiac disorders CHEST PAIN - CARDIAC	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Musculoskeletal and connective tissue disorders CHEST WALL PAIN	14.3% 5/35 • Number of events 6 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
General disorders CHILLS	8.6% 3/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Investigations CHOLESTEROL HIGH	28.6% 10/35 • Number of events 10 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Nervous system disorders COGNITIVE DISTURBANCE	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Nervous system disorders CONCENTRATION IMPAIRMENT	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Psychiatric disorders CONFUSION	5.7% 2/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Gastrointestinal disorders CONSTIPATION	42.9% 15/35 • Number of events 19 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders COUGH	77.1% 27/35 • Number of events 39 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Investigations CREATININE INCREASED	22.9% 8/35 • Number of events 18 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Metabolism and nutrition disorders DEHYDRATION	11.4% 4/35 • Number of events 4 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Psychiatric disorders DEPRESSION	37.1% 13/35 • Number of events 15 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Gastrointestinal disorders DIARRHEA	31.4% 11/35 • Number of events 24 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Nervous system disorders DIZZINESS	20.0% 7/35 • Number of events 9 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Eye disorders DRY EYE	11.4% 4/35 • Number of events 4 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Gastrointestinal disorders DRY MOUTH	11.4% 4/35 • Number of events 4 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Skin and subcutaneous tissue disorders DRY SKIN	8.6% 3/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Nervous system disorders DYSESTHESIA	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Nervous system disorders DYSGEUSIA	20.0% 7/35 • Number of events 9 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Gastrointestinal disorders DYSPEPSIA	8.6% 3/35 • Number of events 4 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Gastrointestinal disorders DYSPHAGIA	5.7% 2/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders DYSPNEA	68.6% 24/35 • Number of events 42 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Ear and labyrinth disorders EAR AND LABYRINTH DISORDERS - OTHER, SPECIFY	2.9% 1/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Ear and labyrinth disorders EAR PAIN	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
General disorders EDEMA FACE	2.9% 1/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
General disorders EDEMA LIMBS	45.7% 16/35 • Number of events 32 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
General disorders EDEMA TRUNK	2.9% 1/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Endocrine disorders ENDOCRINE DISORDERS - OTHER, SPECIFY	5.7% 2/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders EPISTAXIS	8.6% 3/35 • Number of events 5 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Eye disorders EYE DISORDERS - OTHER, SPECIFY	22.9% 8/35 • Number of events 10 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Injury, poisoning and procedural complications FALL	8.6% 3/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
General disorders FATIGUE	74.3% 26/35 • Number of events 73 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Blood and lymphatic system disorders FEBRILE NEUTROPENIA	5.7% 2/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
General disorders FEVER	28.6% 10/35 • Number of events 19 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Musculoskeletal and connective tissue disorders FLANK PAIN	8.6% 3/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
General disorders FLU LIKE SYMPTOMS	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Vascular disorders FLUSHING	5.7% 2/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Injury, poisoning and procedural complications FRACTURE	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
General disorders GAIT DISTURBANCE	2.9% 1/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Gastrointestinal disorders GASTRIC ULCER	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Gastrointestinal disorders GASTRITIS	5.7% 2/35 • Number of events 5 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Gastrointestinal disorders GASTROESOPHAGEAL REFLUX DISEASE	31.4% 11/35 • Number of events 12 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Gastrointestinal disorders GASTROINTESTINAL DISORDERS - OTHER, SPECIFY	11.4% 4/35 • Number of events 4 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
General disorders GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - OTHER, SPECIFY	22.9% 8/35 • Number of events 10 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Musculoskeletal and connective tissue disorders GENERALIZED MUSCLE WEAKNESS	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Nervous system disorders HEADACHE	25.7% 9/35 • Number of events 12 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Ear and labyrinth disorders HEARING IMPAIRED	5.7% 2/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Cardiac disorders HEART FAILURE	5.7% 2/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Renal and urinary disorders HEMATURIA	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Hepatobiliary disorders HEPATOBILIARY DISORDERS - OTHER, SPECIFY	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders HICCUPS	2.9% 1/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders HOARSENESS	5.7% 2/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Vascular disorders HOT FLASHES	8.6% 3/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Metabolism and nutrition disorders HYPERCALCEMIA	11.4% 4/35 • Number of events 4 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Metabolism and nutrition disorders HYPERGLYCEMIA	8.6% 3/35 • Number of events 5 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Metabolism and nutrition disorders HYPERKALEMIA	5.7% 2/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Vascular disorders HYPERTENSION	57.1% 20/35 • Number of events 49 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Endocrine disorders HYPERTHYROIDISM	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Metabolism and nutrition disorders HYPOALBUMINEMIA	14.3% 5/35 • Number of events 12 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Metabolism and nutrition disorders HYPOCALCEMIA	5.7% 2/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Metabolism and nutrition disorders HYPOGLYCEMIA	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Metabolism and nutrition disorders HYPOKALEMIA	11.4% 4/35 • Number of events 4 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Metabolism and nutrition disorders HYPOMAGNESEMIA	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Metabolism and nutrition disorders HYPONATREMIA	28.6% 10/35 • Number of events 22 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Metabolism and nutrition disorders HYPOPHOSPHATEMIA	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Vascular disorders HYPOTENSION	8.6% 3/35 • Number of events 4 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Endocrine disorders HYPOTHYROIDISM	28.6% 10/35 • Number of events 10 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders HYPOXIA	2.9% 1/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Immune system disorders IMMUNE SYSTEM DISORDERS - OTHER, SPECIFY	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Infections and infestations INFECTIONS AND INFESTATIONS - OTHER, SPECIFY	11.4% 4/35 • Number of events 4 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
General disorders INFUSION RELATED REACTION	5.7% 2/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Psychiatric disorders INSOMNIA	42.9% 15/35 • Number of events 17 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Investigations INVESTIGATIONS - OTHER, SPECIFY	5.7% 2/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Musculoskeletal and connective tissue disorders JOINT RANGE OF MOTION DECREASED	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
General disorders LOCALIZED EDEMA	11.4% 4/35 • Number of events 5 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Infections and infestations LUNG INFECTION	5.7% 2/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Infections and infestations LYMPH GLAND INFECTION	5.7% 2/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Investigations LYMPHOCYTE COUNT DECREASED	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
General disorders MALAISE	5.7% 2/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Gastrointestinal disorders MUCOSITIS ORAL	14.3% 5/35 • Number of events 7 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER - OTHER, SPECIFY	22.9% 8/35 • Number of events 8 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Musculoskeletal and connective tissue disorders MYALGIA	14.3% 5/35 • Number of events 8 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Skin and subcutaneous tissue disorders NAIL DISCOLORATION	5.7% 2/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Infections and infestations NAIL INFECTION	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders NASAL CONGESTION	22.9% 8/35 • Number of events 13 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Gastrointestinal disorders NAUSEA	60.0% 21/35 • Number of events 68 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Musculoskeletal and connective tissue disorders NECK PAIN	11.4% 4/35 • Number of events 11 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) - OTHER, SPECIFY	11.4% 4/35 • Number of events 4 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Nervous system disorders NERVOUS SYSTEM DISORDERS - OTHER, SPECIFY	5.7% 2/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Investigations NEUTROPHIL COUNT DECREASED	34.3% 12/35 • Number of events 43 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
General disorders NON-CARDIAC CHEST PAIN	14.3% 5/35 • Number of events 7 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Musculoskeletal and connective tissue disorders OSTEOPOROSIS	8.6% 3/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
General disorders PAIN	31.4% 11/35 • Number of events 21 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	22.9% 8/35 • Number of events 12 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Skin and subcutaneous tissue disorders PAIN OF SKIN	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Nervous system disorders PARESTHESIA	11.4% 4/35 • Number of events 4 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Cardiac disorders PERICARDIAL EFFUSION	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Gastrointestinal disorders PERIODONTAL DISEASE	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Nervous system disorders PERIPHERAL MOTOR NEUROPATHY	2.9% 1/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Nervous system disorders PERIPHERAL SENSORY NEUROPATHY	28.6% 10/35 • Number of events 17 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders PHARYNGEAL MUCOSITIS	2.9% 1/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Vascular disorders PHLEBITIS	8.6% 3/35 • Number of events 4 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Investigations PLATELET COUNT DECREASED	20.0% 7/35 • Number of events 27 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	11.4% 4/35 • Number of events 4 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders PLEURITIC PAIN	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders PNEUMONITIS	8.6% 3/35 • Number of events 7 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders POSTNASAL DRIP	11.4% 4/35 • Number of events 4 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders PRODUCTIVE COUGH	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Reproductive system and breast disorders PROSTATIC OBSTRUCTION	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Skin and subcutaneous tissue disorders PRURITUS	25.7% 9/35 • Number of events 19 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Skin and subcutaneous tissue disorders RASH MACULO-PAPULAR	37.1% 13/35 • Number of events 31 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Gastrointestinal disorders RECTAL MUCOSITIS	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Renal and urinary disorders RENAL AND URINARY DISORDERS - OTHER, SPECIFY	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - OTHER, SPECIFY	34.3% 12/35 • Number of events 13 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Infections and infestations RHINITIS INFECTIVE	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Eye disorders SCLERAL DISORDER	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Nervous system disorders SINUS PAIN	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Infections and infestations SINUSITIS	8.6% 3/35 • Number of events 5 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Skin and subcutaneous tissue disorders SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY	17.1% 6/35 • Number of events 7 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Skin and subcutaneous tissue disorders SKIN HYPERPIGMENTATION	5.7% 2/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Infections and infestations SKIN INFECTION	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders SLEEP APNEA	8.6% 3/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Infections and infestations SOFT TISSUE INFECTION	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Gastrointestinal disorders STOMACH PAIN	5.7% 2/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Vascular disorders SUPERFICIAL THROMBOPHLEBITIS	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Surgical and medical procedures SURGICAL AND MEDICAL PROCEDURES - OTHER, SPECIFY	5.7% 2/35 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Nervous system disorders SYNCOPE	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Vascular disorders THROMBOEMBOLIC EVENT	11.4% 4/35 • Number of events 6 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Infections and infestations TOOTH INFECTION	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Nervous system disorders TREMOR	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) TUMOR PAIN	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Infections and infestations UPPER RESPIRATORY INFECTION	14.3% 5/35 • Number of events 8 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Renal and urinary disorders URINARY FREQUENCY	2.9% 1/35 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Infections and infestations URINARY TRACT INFECTION	8.6% 3/35 • Number of events 5 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Renal and urinary disorders URINARY URGENCY	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Reproductive system and breast disorders VAGINAL DRYNESS	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Reproductive system and breast disorders VAGINAL INFLAMMATION	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Vascular disorders VASCULAR DISORDERS - OTHER, SPECIFY	5.7% 2/35 • Number of events 4 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Ear and labyrinth disorders VERTIGO	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Gastrointestinal disorders VOMITING	37.1% 13/35 • Number of events 26 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Eye disorders WATERING EYES	11.4% 4/35 • Number of events 4 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Investigations WEIGHT GAIN	25.7% 9/35 • Number of events 14 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Investigations WEIGHT LOSS	8.6% 3/35 • Number of events 8 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Respiratory, thoracic and mediastinal disorders WHEEZING	2.9% 1/35 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.
Investigations WHITE BLOOD CELL DECREASED	14.3% 5/35 • Number of events 29 • All-Cause Mortality was monitored up to a maximum of 40 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored from the initiation of study therapy until 30 days after treatment discontinuation, up to 25 months.

Additional Information

Fauzia Sharmin

Hoosier Cancer Research Network

Phone: (317) 634-5842

Email: fsharmin@hoosiercancer.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place