Trial Outcomes & Findings for Pembrolizumab in Refractory Advanced Esophageal Cancer (NCT NCT02971956)

NCT ID: NCT02971956

Last Updated: 2023-09-21

Results Overview

The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 49 participants
• Primary outcome timeframe: Disease was evaluated each cycle on treatment; Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 2.1 months with a maximum of 14.9 months.
• Results posted on: 2023-09-21

Participant Flow

from January 2017 to October 2018

Participant milestones

Measure	Pembrolizumab Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
Overall Study STARTED	49
Overall Study COMPLETED	49
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pembrolizumab in Refractory Advanced Esophageal Cancer

Baseline characteristics by cohort

Measure	Pembrolizumab n=49 Participants Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
Age, Customized	64 years n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Race/Ethnicity, Customized White	44 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants
Race/Ethnicity, Customized More than one race	1 Participants n=5 Participants
Region of Enrollment United States	49 participants n=5 Participants

PRIMARY outcome

Timeframe: Disease was evaluated each cycle on treatment; Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 2.1 months with a maximum of 14.9 months.

The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Outcome measures

Measure	Pembrolizumab n=49 Participants Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
Overall Response Rate (ORR)	0.08 proportion of participant Interval 0.023 to 0.196

SECONDARY outcome

Timeframe: Disease was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 28.9 months

Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

Outcome measures

Measure	Pembrolizumab n=49 Participants Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
Median Progression-free Survival (PFS)	1.8 months Interval 1.8 to 2.0

SECONDARY outcome

Timeframe: Disease was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months.

OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

Outcome measures

Measure	Pembrolizumab n=49 Participants Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
Median Overall Survival (OS)	5.8 months Interval 4.0 to 9.5

SECONDARY outcome

Timeframe: Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months.

All grade 3-4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Outcome defined as the number of patients experiencing at least one treatment-related grade 3-4 AE of any type during the time of observation.

Outcome measures

Measure	Pembrolizumab n=49 Participants Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
Number of Patients Experiencing Grade 3-4 Treatment-Related Toxicity	6 Participants

Adverse Events

Pembrolizumab

Serious events: 6 serious events

Other events: 46 other events

Deaths: 49 deaths

Serious adverse events

Measure	Pembrolizumab n=49 participants at risk Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
Cardiac disorders Cardiac arrest	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Eye disorders Eye disorders - Other	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Duodenal hemorrhage	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Dysphagia	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
General disorders Pain	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Aspartate aminotransferase increased	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Anorexia	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Arthralgia	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Myalgia	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Nervous system disorders - Other	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Pneumonitis	4.1% 2/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.

Other adverse events

Measure	Pembrolizumab n=49 participants at risk Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
Blood and lymphatic system disorders Anemia	65.3% 32/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Cardiac disorders Atrial fibrillation	4.1% 2/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Cardiac disorders Chest pain - cardiac	4.1% 2/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Cardiac disorders Palpitations	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Cardiac disorders Sinus tachycardia	16.3% 8/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Endocrine disorders Endocrine disorders - Other	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Endocrine disorders Hyperthyroidism	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Endocrine disorders Hypothyroidism	6.1% 3/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Eye disorders Eye disorders - Other	4.1% 2/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Eye disorders Vitreous hemorrhage	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Abdominal distension	4.1% 2/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Abdominal pain	30.6% 15/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Ascites	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Constipation	34.7% 17/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Diarrhea	28.6% 14/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Dry mouth	6.1% 3/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Duodenal hemorrhage	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Dyspepsia	8.2% 4/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Dysphagia	36.7% 18/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Esophageal hemorrhage	4.1% 2/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Esophageal pain	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Esophageal perforation	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Fecal incontinence	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Gastric hemorrhage	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Gastritis	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Gastrointestinal disorders - Other	6.1% 3/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Gastrointestinal pain	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Mucositis oral	4.1% 2/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Nausea	40.8% 20/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Obstruction gastric	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Pancreatitis	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Vomiting	24.5% 12/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
General disorders Death NOS	6.1% 3/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
General disorders Edema limbs	14.3% 7/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
General disorders Fatigue	81.6% 40/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
General disorders Fever	6.1% 3/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
General disorders Gait disturbance	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
General disorders General disorders and administration site conditions - Other	6.1% 3/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
General disorders Localized edema	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
General disorders Non-cardiac chest pain	8.2% 4/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
General disorders Pain	14.3% 7/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Infections and infestations Abdominal infection	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Infections and infestations Bronchial infection	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Infections and infestations Lung infection	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Activated partial thromboplastin time prolonged	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Alanine aminotransferase increased	16.3% 8/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Alkaline phosphatase increased	53.1% 26/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Aspartate aminotransferase increased	40.8% 20/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Blood bilirubin increased	14.3% 7/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Creatinine increased	6.1% 3/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Investigations - Other	4.1% 2/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Lipase increased	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Lymphocyte count decreased	6.1% 3/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Neutrophil count decreased	10.2% 5/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Platelet count decreased	24.5% 12/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Weight gain	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Weight loss	20.4% 10/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations White blood cell decreased	8.2% 4/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Acidosis	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Anorexia	42.9% 21/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Dehydration	16.3% 8/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypercalcemia	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hyperglycemia	63.3% 31/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hyperkalemia	6.1% 3/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypernatremia	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypoalbuminemia	63.3% 31/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypocalcemia	6.1% 3/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypokalemia	14.3% 7/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypomagnesemia	4.1% 2/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hyponatremia	49.0% 24/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Arthralgia	8.2% 4/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Arthritis	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Back pain	32.7% 16/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Bone pain	6.1% 3/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Chest wall pain	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	16.3% 8/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	6.1% 3/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Myalgia	4.1% 2/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Neck pain	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Pain in extremity	12.2% 6/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Ataxia	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Dizziness	16.3% 8/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Dysgeusia	6.1% 3/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Headache	4.1% 2/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Memory impairment	4.1% 2/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Nervous system disorders - Other	10.2% 5/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Peripheral motor neuropathy	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Peripheral sensory neuropathy	20.4% 10/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Syncope	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Tremor	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Anxiety	8.2% 4/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Confusion	14.3% 7/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Depression	6.1% 3/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Insomnia	12.2% 6/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Renal and urinary disorders Hematuria	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Renal and urinary disorders Proteinuria	4.1% 2/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Renal and urinary disorders Renal and urinary disorders - Other	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Cough	42.9% 21/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Dyspnea	34.7% 17/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Epistaxis	6.1% 3/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.1% 2/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other	6.1% 3/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Tracheal fistula	8.2% 4/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Alopecia	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Dry skin	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Hyperhidrosis	8.2% 4/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Pruritus	10.2% 5/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Rash acneiform	4.1% 2/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Rash maculo-papular	14.3% 7/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	8.2% 4/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Vascular disorders Hypertension	59.2% 29/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Vascular disorders Hypotension	4.1% 2/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Vascular disorders Thromboembolic event	6.1% 3/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Vascular disorders Vascular disorders - Other	2.0% 1/49 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.

Additional Information

Peter C. Enzinger MD

Dana-Farber Cancer Institute

Phone: (877) 442-3324

Email: Peter_Enzinger@dfci.harvard.edu

Results disclosure agreements

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