Trial Outcomes & Findings for Durvalumab and Tremelimumab in Patients With Advanced Rare Tumours (NCT NCT02879162)

Last Updated: 2025-03-07

Results Overview

Objective response rate is defined as the proportion of response evaluable patients who had complete response (CR) or partial response (PR) as their best response as assessed by RECIST version 1.1 criteria (i.e. a 30% decrease in the sum of the longest diameters of the target lesions maintained for at least 4 weeks (CR), or complete disappearance of disease and cancer related symptoms, also maintained for at least 4 weeks (CR)).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

140 participants

Primary outcome timeframe

48 months

Results posted on

2025-03-07

Participant Flow

Participant milestones

Participant milestones
Measure	Durvalumab + Tremelimumab Durvalumab 1500 mg IV 60 min Day 1 every 4 weeks Tremelimumab 75 mg IV 60 min Day 1, cycles 1-4 Durvalumab Tremelimumab
Overall Study STARTED	140
Overall Study COMPLETED	138
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Durvalumab and Tremelimumab in Patients With Advanced Rare Tumours

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Durvalumab + Tremelimumab n=138 Participants Durvalumab 1500 mg IV 60 min Day 1 every 4 weeks Tremelimumab 75 mg IV 60 min Day 1, cycles 1-4 Durvalumab Tremelimumab
Age, Continuous	59.4 years n=99 Participants
Sex: Female, Male Female	82 Participants n=99 Participants
Sex: Female, Male Male	56 Participants n=99 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=99 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	135 Participants n=99 Participants
Race/Ethnicity, Customized Unknown	2 Participants n=99 Participants

PRIMARY outcome

Timeframe: 48 months

Outcome measures

Outcome measures
Measure	Durvalumab + Tremelimumab n=136 Participants Durvalumab 1500 mg IV 60 min Day 1 every 4 weeks Tremelimumab 75 mg IV 60 min Day 1, cycles 1-4 Durvalumab Tremelimumab
Objective Response Rate Measured by RECIST Version 1.1 CR	1 Participants
Objective Response Rate Measured by RECIST Version 1.1 PR	19 Participants
Objective Response Rate Measured by RECIST Version 1.1 SD	32 Participants
Objective Response Rate Measured by RECIST Version 1.1 PD	76 Participants
Objective Response Rate Measured by RECIST Version 1.1 IN	8 Participants

SECONDARY outcome

Timeframe: 48 months

defined as time from the date of randomization to the date of progression

Outcome measures

Outcome measures
Measure	Durvalumab + Tremelimumab n=136 Participants Durvalumab 1500 mg IV 60 min Day 1 every 4 weeks Tremelimumab 75 mg IV 60 min Day 1, cycles 1-4 Durvalumab Tremelimumab
Time to Progression Based on Kaplan-Meier Method	2.8 months Interval 2.6 to 2.9

SECONDARY outcome

Timeframe: 48 months

defined as time from the date of randomization to the date of progression or death

Outcome measures

Outcome measures
Measure	Durvalumab + Tremelimumab n=136 Participants Durvalumab 1500 mg IV 60 min Day 1 every 4 weeks Tremelimumab 75 mg IV 60 min Day 1, cycles 1-4 Durvalumab Tremelimumab
Progression Free Survival Based on Kaplan-Meier Method	2.8 months Interval 2.6 to 2.8

Adverse Events

Durvalumab + Tremelimumab

Serious events: 80 serious events

Other events: 137 other events

Deaths: 114 deaths

Serious adverse events

Serious adverse events
Measure	Durvalumab + Tremelimumab n=138 participants at risk Durvalumab 1500 mg IV 60 min Day 1 every 4 weeks Tremelimumab 75 mg IV 60 min Day 1, cycles 1-4 Durvalumab Tremelimumab
General disorders Fatigue	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Infections and infestations - Other specify	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Pain	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Skin infection	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Diarrhea	9.4% 13/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.5% 9/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Colitis	5.8% 8/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign malignant and unspecified (incl cysts and polyps) - Other specify	5.8% 8/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Investigations Alanine aminotransferase increased	4.3% 6/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Investigations Aspartate aminotransferase increased	4.3% 6/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Immune system disorders Immune system disorders - Other specify	4.3% 6/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Rash maculo-papular	4.3% 6/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Vomiting	3.6% 5/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Renal and urinary disorders Acute kidney injury	2.9% 4/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Fever	2.9% 4/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Small intestinal obstruction	2.9% 4/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Blood and lymphatic system disorders Anemia	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Arthralgia	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Investigations Blood bilirubin increased	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Vascular disorders Thromboembolic event	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Abdominal infection	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Abdominal pain	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Ascites	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Aspiration	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Cardiac disorders Atrial fibrillation	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Avascular necrosis	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Back pain	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Syncope	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Bone pain	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Cardiac disorders Cardiac disorders - Other specify	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Injury, poisoning and procedural complications Tracheal obstruction	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Cecal hemorrhage	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Investigations Creatinine increased	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Metabolism and nutrition disorders Dehydration	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Device related infection	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Edema limbs	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Injury, poisoning and procedural complications Fracture	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Gastrointestinal disorders - Other specify	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Hepatobiliary disorders Hepatobiliary disorders - Other specify	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Injury, poisoning and procedural complications Hip fracture	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Metabolism and nutrition disorders Hypercalcemia	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Upper respiratory infection	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Metabolism and nutrition disorders Hyperkalemia	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Metabolism and nutrition disorders Hypokalemia	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Vascular disorders Hypotension	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Endocrine disorders Hypothyroidism	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Ileus	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Injury, poisoning and procedural complications Intestinal stoma obstruction	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukemia secondary to oncology chemotherapy	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Investigations Lipase increased	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Lung infection	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Myositis	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Nausea	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Nervous system disorders - Other specify	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Investigations Neutrophil count decreased	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Pancreatitis	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Peripheral motor neuropathy	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Presyncope	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Proctitis	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Renal and urinary disorders Renal and urinary disorders - Other specify	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Renal and urinary disorders Renal colic	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Respiratory thoracic and mediastinal disorders - Other specify	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Seizure	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Sepsis	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Small intestinal perforation	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Sudden death NOS	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Urinary tract infection	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Investigations White blood cell decreased	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Wound infection	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.

Other adverse events

Other adverse events
Measure	Durvalumab + Tremelimumab n=138 participants at risk Durvalumab 1500 mg IV 60 min Day 1 every 4 weeks Tremelimumab 75 mg IV 60 min Day 1, cycles 1-4 Durvalumab Tremelimumab
General disorders Fatigue	79.0% 109/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Diarrhea	46.4% 64/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Nausea	44.2% 61/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	44.2% 61/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Metabolism and nutrition disorders Anorexia	42.8% 59/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Constipation	41.3% 57/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Cough	38.4% 53/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Abdominal pain	34.1% 47/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Pruritus	31.2% 43/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Rash maculo-papular	30.4% 42/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Back pain	29.0% 40/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Vomiting	26.8% 37/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Pain in extremity	22.5% 31/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Headache	21.0% 29/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Endocrine disorders Hypothyroidism	20.3% 28/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Edema limbs	20.3% 28/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Pain	20.3% 28/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Psychiatric disorders Insomnia	19.6% 27/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Peripheral sensory neuropathy	18.8% 26/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Arthralgia	17.4% 24/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Fever	15.9% 22/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other specify	15.2% 21/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Dry mouth	13.8% 19/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Dizziness	13.8% 19/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Vascular disorders Hot flashes	13.0% 18/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Flu like symptoms	10.9% 15/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Dyspepsia	10.1% 14/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Non-cardiac chest pain	10.1% 14/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Myalgia	10.1% 14/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Vascular disorders Thromboembolic event	9.4% 13/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Upper respiratory infection	8.7% 12/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Urinary tract infection	8.7% 12/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Psychiatric disorders Anxiety	8.7% 12/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Dry skin	8.7% 12/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Cardiac disorders Sinus tachycardia	8.0% 11/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Dysphagia	8.0% 11/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Dysgeusia	8.0% 11/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Alopecia	8.0% 11/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Gastroesophageal reflux disease	7.2% 10/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Neck pain	7.2% 10/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Endocrine disorders Hyperthyroidism	6.5% 9/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Gastrointestinal disorders - Other specify	6.5% 9/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Mucositis oral	6.5% 9/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Nervous system disorders - Other specify	6.5% 9/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Eye disorders Dry eye	5.8% 8/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Eye disorders Eye disorders - Other specify	5.8% 8/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Bloating	5.8% 8/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.8% 8/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Oral pain	5.1% 7/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Chills	5.1% 7/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders General disorders and administration site conditions - Other specify	5.1% 7/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Renal and urinary disorders Urinary frequency	5.1% 7/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Productive cough	5.1% 7/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Rectal pain	4.3% 6/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Metabolism and nutrition disorders Dehydration	4.3% 6/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Flank pain	4.3% 6/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	4.3% 6/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other specify	4.3% 6/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Paresthesia	4.3% 6/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Somnolence	4.3% 6/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Psychiatric disorders Depression	4.3% 6/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Renal and urinary disorders Renal and urinary disorders - Other specify	4.3% 6/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Hyperhidrosis	4.3% 6/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Vascular disorders Hypertension	4.3% 6/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Vascular disorders Lymphedema	4.3% 6/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Ear and labyrinth disorders Ear and labyrinth disorders - Other specify	3.6% 5/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Eye disorders Blurred vision	3.6% 5/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Rectal hemorrhage	3.6% 5/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Immune system disorders Immune system disorders - Other specify	3.6% 5/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Infections and infestations - Other specify	3.6% 5/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Injury, poisoning and procedural complications Fall	3.6% 5/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Bone pain	3.6% 5/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Psychiatric disorders Confusion	3.6% 5/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Hoarseness	3.6% 5/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Respiratory thoracic and mediastinal disorders - Other specify	3.6% 5/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Ear and labyrinth disorders Tinnitus	2.9% 4/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Flatulence	2.9% 4/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Edema face	2.9% 4/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Immune system disorders Allergic reaction	2.9% 4/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Injury, poisoning and procedural complications Bruising	2.9% 4/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Injury, poisoning and procedural complications Fracture	2.9% 4/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Chest wall pain	2.9% 4/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	2.9% 4/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	2.9% 4/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Neuralgia	2.9% 4/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Reproductive system and breast disorders Pelvic pain	2.9% 4/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Reproductive system and breast disorders Vaginal discharge	2.9% 4/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.9% 4/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Blood and lymphatic system disorders Anemia	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other specify	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Ear and labyrinth disorders Hearing impaired	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Endocrine disorders Adrenal insufficiency	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Endocrine disorders Cushingoid	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Eye disorders Conjunctivitis	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Eye disorders Eye pain	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Eye disorders Floaters	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Colitis	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Lung infection	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Skin infection	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Investigations Alanine aminotransferase increased	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Metabolism and nutrition disorders Hyponatremia	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Dysphasia	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Memory impairment	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Peripheral motor neuropathy	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Reproductive system and breast disorders Reproductive system and breast disorders - Other specify	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Sore throat	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Wheezing	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Rash acneiform	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Vascular disorders Hypotension	2.2% 3/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Ear and labyrinth disorders Ear pain	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Eye disorders Watering eyes	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Anal pain	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Stomach pain	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Edema trunk	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Infusion related reaction	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Localized edema	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Rhinitis infective	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Sinusitis	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Wound infection	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Injury, poisoning and procedural complications Injury poisoning and procedural complications - Other specify	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Injury, poisoning and procedural complications Wound complication	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Investigations Aspartate aminotransferase increased	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Investigations Cholesterol high	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Investigations Investigations - Other specify	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Metabolism and nutrition disorders Hypercalcemia	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Metabolism and nutrition disorders Hypophosphatemia	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Myositis	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Depressed level of consciousness	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Phantom pain	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Presyncope	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Seizure	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Tremor	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Renal and urinary disorders Acute kidney injury	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Renal and urinary disorders Hematuria	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Renal and urinary disorders Proteinuria	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Renal and urinary disorders Urinary incontinence	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Reproductive system and breast disorders Vaginal hemorrhage	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Reproductive system and breast disorders Vaginal pain	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Postnasal drip	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Voice alteration	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Urticaria	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Vascular disorders Hematoma	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Vascular disorders Vascular disorders - Other specify	1.4% 2/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Blood and lymphatic system disorders Febrile neutropenia	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Blood and lymphatic system disorders Lymph node pain	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Cardiac disorders Atrial fibrillation	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Cardiac disorders Palpitations	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Cardiac disorders Ventricular arrhythmia	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Ear and labyrinth disorders Vertigo	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Endocrine disorders Endocrine disorders - Other specify	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Eye disorders Eyelid function disorder	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Eye disorders Flashing lights	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Abdominal distension	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Ascites	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Gastrointestinal pain	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Hemorrhoidal hemorrhage	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Hemorrhoids	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Oral hemorrhage	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Pancreatitis	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Proctitis	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Small intestinal obstruction	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Gastrointestinal disorders Toothache	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Facial pain	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Gait disturbance	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Injection site reaction	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Irritability	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
General disorders Malaise	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Hepatobiliary disorders Portal vein thrombosis	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Abdominal infection	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Bladder infection	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Eye infection	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Infective myositis	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Lymph gland infection	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Mucosal infection	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Otitis media	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Paronychia	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Rash pustular	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Soft tissue infection	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Infections and infestations Vaginal infection	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Injury, poisoning and procedural complications Intestinal stoma site bleeding	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Investigations Alkaline phosphatase increased	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Investigations CPK increased	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Investigations Cardiac troponin T increased	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Investigations Weight loss	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Metabolism and nutrition disorders Glucose intolerance	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Metabolism and nutrition disorders Hyperglycemia	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Metabolism and nutrition disorders Hyperuricemia	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Metabolism and nutrition disorders Hypokalemia	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Buttock pain	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Muscle weakness trunk	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign malignant and unspecified (incl cysts and polyps) - Other specify	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Ataxia	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Cognitive disturbance	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Dysarthria	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Dysesthesia	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Movements involuntary	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Nervous system disorders Transient ischemic attacks	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Psychiatric disorders Delirium	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Psychiatric disorders Restlessness	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Renal and urinary disorders Cystitis noninfective	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Renal and urinary disorders Renal colic	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Renal and urinary disorders Urinary tract pain	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Renal and urinary disorders Urinary urgency	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Reproductive system and breast disorders Breast pain	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Reproductive system and breast disorders Dyspareunia	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Reproductive system and breast disorders Genital edema	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Reproductive system and breast disorders Perineal pain	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Reproductive system and breast disorders Testicular disorder	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Reproductive system and breast disorders Testicular pain	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Hiccups	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Body odor	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Bullous dermatitis	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Erythema multiforme	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Hypertrichosis	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Hypohidrosis	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Lipohypertrophy	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Nail ridging	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Photosensitivity	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Scalp pain	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Skin and subcutaneous tissue disorders Skin induration	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.
Vascular disorders Flushing	0.72% 1/138 • Continuously measured at baseline, day 1 of each cycle, and as clinically indicated, 4 week after completion of protocol therapy, every three months thereafter to follow adverse events felt related until resolved to ≤ Grade 2, to 48 months.

Additional Information

Dr. Janet Dancey

Canadian Cancer Trials Group

Phone: 6135336000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place