Trial Outcomes & Findings for Study of TAK-228 In Patients With Previously Treated Metastatic Renal Cell Carcinoma (NCT NCT03097328)

Last Updated: 2024-04-29

Results Overview

The best overall response rate is the percentage of participants achieving complete response (CR) or partial response (PR) as the best response recorded on treatment based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1). CR and PR must meet the following lesion criteria without having any new lesions as well: Target Lesion: (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Non-Target Lesion: (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). Non-CR/Non-Progressive Disease: Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. Must have PR in target lesion.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

39 participants

Primary outcome timeframe

Imaging assessments occurred every eight weeks (2 cycles) for response evaluation. The median number of cycles administered was 2 (range <1-15), thus participants were assessed up to ~14 months.

Results posted on

2024-04-29

Participant Flow

39 patients were enrolled from 8 institutions between August 2017 and November 2019.

1 patient was deemed as ineligible and did not receive protocol treatment. 38 eligible and treated patients were included in the analysis.

Participant milestones

Participant milestones
Measure	TAK-228 Subjects will receive treatment with TAK-228 30mg by mouth weekly on day 1, 8, 15 and 22 of a 28-day cycle. Dose can be reduced by the study team. Treatment will continue until disease progression, unaccepted toxicity or other reasons for discontinuation defined by protocol.
Overall Study STARTED	39
Overall Study Treated	38
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	39

Reasons for withdrawal

Reasons for withdrawal
Measure	TAK-228 Subjects will receive treatment with TAK-228 30mg by mouth weekly on day 1, 8, 15 and 22 of a 28-day cycle. Dose can be reduced by the study team. Treatment will continue until disease progression, unaccepted toxicity or other reasons for discontinuation defined by protocol.
Overall Study Still on Therapy	2
Overall Study Progressive Disease	29
Overall Study Adverse Event	4
Overall Study Withdrawal by Subject	1
Overall Study Physician Decision	1
Overall Study Patient Decision	1
Overall Study Ineligible for Study Drug	1

Baseline Characteristics

Study of TAK-228 In Patients With Previously Treated Metastatic Renal Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TAK228 n=38 Participants Subjects will receive treatment with TAK-228 30mg by mouth weekly on day 1, 8, 15 and 22 of a 28-day cycle. Dose can be reduced by the study team. Treatment will continue until disease progression, unaccepted toxicity or other reasons for discontinuation defined by protocol.
Age, Continuous	62 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	33 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	36 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Histology Clear cell histology	28 Participants n=5 Participants
Histology Non clear cell histology	10 Participants n=5 Participants
Prior rapalogs treatment No	21 Participants n=5 Participants
Prior rapalogs treatment Yes	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: Imaging assessments occurred every eight weeks (2 cycles) for response evaluation. The median number of cycles administered was 2 (range <1-15), thus participants were assessed up to ~14 months.

Population: Best overall response was assessed in 38 eligible and treated patients. 1 patient who was deemed as ineligible and did not receive treatment was excluded from response analysis.

Outcome measures

Outcome measures
Measure	TAK-228 n=38 Participants Subjects will receive treatment with TAK-228 30mg by mouth weekly on day 1, 8, 15 and 22 of a 28-day cycle. Dose can be reduced by the study team. Treatment will continue until disease progression, unaccepted toxicity or other reasons for discontinuation defined by protocol.
Best Overall Response Rate	5 percentage of participants Interval 1.0 to 16.0

SECONDARY outcome

Timeframe: Participants followed for up to 14 months

Population: Progression free survival was assessed in 38 eligible and treated patients. 1 patient who was deemed as ineligible and did not receive treatment was excluded from analysis.

Progression free survival (PFS) was defined as time from treatment initiation to radiographic progression, clinical progression or death from any cause, or it was censored at the date of last disease evaluation if an event had not occurred. Median PFS was estimated from the Kaplan Meier methodology. Radiographic progression is defined by Response Evaluation Criteria In Solid Tumors Criteria 1.1 as follows: \- \>20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including baseline if it's the smallest). OR -Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	TAK-228 n=38 Participants Subjects will receive treatment with TAK-228 30mg by mouth weekly on day 1, 8, 15 and 22 of a 28-day cycle. Dose can be reduced by the study team. Treatment will continue until disease progression, unaccepted toxicity or other reasons for discontinuation defined by protocol.
Median Progression Free Survival	2.5 months Interval 1.8 to 3.7

SECONDARY outcome

Timeframe: Participants were follow for up to ~27 months

Population: Overall survival was assessed in 38 eligible and treated patients. 1 patient who was deemed as ineligible and did not receive treatment was excluded from analysis.

Overall survival was defined as the time from treatment initiation to death from any cause or censored at the time of last follow-up for surviving patients. Median overall survival was estimated using the Kaplan Meier methodology.

Outcome measures

Outcome measures
Measure	TAK-228 n=38 Participants Subjects will receive treatment with TAK-228 30mg by mouth weekly on day 1, 8, 15 and 22 of a 28-day cycle. Dose can be reduced by the study team. Treatment will continue until disease progression, unaccepted toxicity or other reasons for discontinuation defined by protocol.
Median Overall Survival	11.2 months Interval 1.0 to 27.4

SECONDARY outcome

Timeframe: Adverse events are measured continuously on treatment and up to thirty days after going off treatment (up to ~15 months).

Population: Adverse events were assessed in 38 eligible and treated patients. 1 patient who was deemed as ineligible and did not receive treatment was excluded from analysis.

Toxicity was assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Treatment related adverse events were those that were deemed as "Definitely", "Probably" and "Possibly" related to the study treatment.

Outcome measures

Outcome measures
Measure	TAK-228 n=38 Participants Subjects will receive treatment with TAK-228 30mg by mouth weekly on day 1, 8, 15 and 22 of a 28-day cycle. Dose can be reduced by the study team. Treatment will continue until disease progression, unaccepted toxicity or other reasons for discontinuation defined by protocol.
Percentage of Participants With Any Grade 3 or Higher Treatment-related Adverse Events Number of subjects who experienced grade 3 or higher adverse events	12 Participants
Percentage of Participants With Any Grade 3 or Higher Treatment-related Adverse Events Number of subjects who did not experience grade 3 or higher adverse events	26 Participants

Adverse Events

TAK-228

Serious events: 12 serious events

Other events: 38 other events

Deaths: 15 deaths

Serious adverse events

Serious adverse events
Measure	TAK-228 n=38 participants at risk Subjects will receive treatment with TAK-228 30mg by mouth weekly on day 1, 8, 15 and 22 of a 28-day cycle. Dose can be reduced by the study team. Treatment will continue until disease progression, unaccepted toxicity or other reasons for discontinuation defined by protocol
Cardiac disorders Myocardial infarction	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Mucositis oral	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Nausea	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Vomiting	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
General disorders Fatigue	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Metabolism and nutrition disorders Anorexia	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Metabolism and nutrition disorders Dehydration	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Metabolism and nutrition disorders Hyperglycemia	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Metabolism and nutrition disorders Hyperkalemia	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Metabolism and nutrition disorders Hyponatremia	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Renal and urinary disorders Chronic kidney disease	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Skin and subcutaneous tissue disorders Rash maculo-papular	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Vascular disorders Vascular disorders - Other, specify	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.

Other adverse events

Other adverse events
Measure	TAK-228 n=38 participants at risk Subjects will receive treatment with TAK-228 30mg by mouth weekly on day 1, 8, 15 and 22 of a 28-day cycle. Dose can be reduced by the study team. Treatment will continue until disease progression, unaccepted toxicity or other reasons for discontinuation defined by protocol
Blood and lymphatic system disorders Anemia	23.7% 9/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Blood and lymphatic system disorders Leukocytosis	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Blood and lymphatic system disorders Lymph node pain	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Cardiac disorders Atrioventricular block first degree	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Cardiac disorders Chest pain - cardiac	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Cardiac disorders Palpitations	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Cardiac disorders Sinus bradycardia	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Cardiac disorders Sinus tachycardia	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Cardiac disorders Cardiac disorders - Other, specify	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Ear and labyrinth disorders Tinnitus	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Endocrine disorders Adrenal insufficiency	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Endocrine disorders Hyperparathyroidism	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Endocrine disorders Hyperthyroidism	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Endocrine disorders Hypothyroidism	10.5% 4/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Endocrine disorders Endocrine disorders - Other, specify	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Eye disorders Eye pain	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Eye disorders Retinal detachment	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Eye disorders Watering eyes	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Abdominal distension	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Abdominal pain	7.9% 3/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Anal pain	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Colitis	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Constipation	39.5% 15/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Diarrhea	23.7% 9/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Dry mouth	10.5% 4/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Duodenal hemorrhage	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Dyspepsia	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Gastroesophageal reflux disease	10.5% 4/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Mucositis oral	31.6% 12/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Nausea	68.4% 26/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Small intestinal obstruction	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Stomach pain	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Toothache	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Vomiting	34.2% 13/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	7.9% 3/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
General disorders Chills	7.9% 3/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
General disorders Edema limbs	10.5% 4/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
General disorders Fatigue	63.2% 24/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
General disorders Fever	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
General disorders Gait disturbance	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
General disorders Non-cardiac chest pain	7.9% 3/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
General disorders Pain	18.4% 7/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
General disorders General disorders and administration site conditions - Other, specify	7.9% 3/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Hepatobiliary disorders Bile duct stenosis	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Infections and infestations Nail infection	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Infections and infestations Sinusitis	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Infections and infestations Upper respiratory infection	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Infections and infestations Urinary tract infection	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Infections and infestations Vaginal infection	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Injury, poisoning and procedural complications Bruising	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Injury, poisoning and procedural complications Fracture	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Investigations Alanine aminotransferase increased	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Investigations Aspartate aminotransferase increased	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Investigations Blood bilirubin increased	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Investigations Cholesterol high	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Investigations Creatinine increased	15.8% 6/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Investigations Lymphocyte count decreased	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Investigations Platelet count decreased	7.9% 3/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Investigations Weight loss	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Investigations Investigations - Other, specify	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Metabolism and nutrition disorders Anorexia	42.1% 16/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Metabolism and nutrition disorders Dehydration	10.5% 4/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Metabolism and nutrition disorders Hypercalcemia	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Metabolism and nutrition disorders Hyperglycemia	13.2% 5/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Metabolism and nutrition disorders Hyperkalemia	18.4% 7/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Metabolism and nutrition disorders Hypertriglyceridemia	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Metabolism and nutrition disorders Hypokalemia	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Metabolism and nutrition disorders Hyponatremia	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Musculoskeletal and connective tissue disorders Abdominal soft tissue necrosis	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Musculoskeletal and connective tissue disorders Arthralgia	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Musculoskeletal and connective tissue disorders Back pain	21.1% 8/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Musculoskeletal and connective tissue disorders Bone pain	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Musculoskeletal and connective tissue disorders Buttock pain	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Musculoskeletal and connective tissue disorders Flank pain	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	10.5% 4/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Musculoskeletal and connective tissue disorders Myalgia	13.2% 5/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Musculoskeletal and connective tissue disorders Pain in extremity	18.4% 7/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Nervous system disorders Amnesia	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Nervous system disorders Dizziness	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Nervous system disorders Dysgeusia	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Nervous system disorders Headache	10.5% 4/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Nervous system disorders Memory impairment	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Nervous system disorders Peripheral motor neuropathy	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Nervous system disorders Seizure	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Nervous system disorders Tremor	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Nervous system disorders Nervous system disorders - Other, specify	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Psychiatric disorders Agitation	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Psychiatric disorders Anxiety	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Psychiatric disorders Confusion	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Psychiatric disorders Delirium	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Psychiatric disorders Depression	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Psychiatric disorders Insomnia	7.9% 3/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Psychiatric disorders Suicidal ideation	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Renal and urinary disorders Acute kidney injury	7.9% 3/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Renal and urinary disorders Hematuria	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Renal and urinary disorders Hemoglobinuria	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Renal and urinary disorders Proteinuria	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Renal and urinary disorders Urinary frequency	7.9% 3/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Renal and urinary disorders Urinary retention	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Renal and urinary disorders Urinary tract obstruction	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Renal and urinary disorders Renal and urinary disorders - Other, specify	10.5% 4/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Reproductive system and breast disorders Breast pain	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Respiratory, thoracic and mediastinal disorders Apnea	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Respiratory, thoracic and mediastinal disorders Cough	26.3% 10/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Respiratory, thoracic and mediastinal disorders Dyspnea	18.4% 7/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Respiratory, thoracic and mediastinal disorders Hiccups	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Respiratory, thoracic and mediastinal disorders Sore throat	10.5% 4/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Respiratory, thoracic and mediastinal disorders Tracheal fistula	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Skin and subcutaneous tissue disorders Bullous dermatitis	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Skin and subcutaneous tissue disorders Dry skin	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Skin and subcutaneous tissue disorders Hyperhidrosis	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Skin and subcutaneous tissue disorders Pruritus	13.2% 5/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Skin and subcutaneous tissue disorders Rash maculo-papular	23.7% 9/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	7.9% 3/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Surgical and medical procedures Surgical and medical procedures - Other, specify	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Vascular disorders Hematoma	5.3% 2/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Vascular disorders Hypertension	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Vascular disorders Hypotension	13.2% 5/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Vascular disorders Thromboembolic event	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.
Vascular disorders Vascular disorders - Other, specify	2.6% 1/38 • Adverse events were assessed from registration to 30 days after end of treatment, up to 15 months. All-Cause Mortality assessed up to approximately 27 months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets.

Additional Information

Bradley McGregor, MD

Dana Farber Cancer Institute

Phone: 617-632-6328

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place