Trial Outcomes & Findings for A Phase II Study of Ramucirumab With Somatostatin Analog Therapy in Patients With Advanced, Progressive Carcinoid Tumors (NCT NCT02795858)

Last Updated: 2025-02-19

Results Overview

To assess the progression-free survival duration of patients with advanced, progressive carcinoid tumors treated with ramucirumab in combination with somatostatin analog therapy. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) was used. Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study with at least a 5 mm absolute increase in the sum of all lesions. The appearance of one or more new lesions denotes disease progression. Partial Response (PR) is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

43 participants

Primary outcome timeframe

Survival collected every 12 weeks in long-term follow-up. The median survival follow-up time was 23.5 months (range 1.7 - 76.6 months)

Results posted on

2025-02-19

Participant Flow

Participant milestones

Participant milestones
Measure	Ramucirumab In Combination With Somatostatin Analog Patients will receive treatment with Ramucirumab at a dose of 8mg/kg intravenously every 14 days of a 28-day treatment cycle. Patients will receive treatment with a Somatostatin Analog at a pre-determined dose.
Overall Study STARTED	43
Overall Study COMPLETED	43
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase II Study of Ramucirumab With Somatostatin Analog Therapy in Patients With Advanced, Progressive Carcinoid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ramucirumab In Combination With Somatostatin Analog n=43 Participants Patients will receive treatment with Ramucirumab at a pre-determined dose intravenously every 14 days of a 28-day treatment cycle. Patients will receive treatment with a Somatostatin Analog at a pre-determined dose.
Age, Continuous	64 years n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	41 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	43 Participants n=5 Participants
Primary Tumor Location Small Intestine	20 Participants n=5 Participants
Primary Tumor Location Lung	10 Participants n=5 Participants
Primary Tumor Location Thymus	3 Participants n=5 Participants
Primary Tumor Location Rectum	1 Participants n=5 Participants
Primary Tumor Location Kidney	1 Participants n=5 Participants
Primary Tumor Location Unknown	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Survival collected every 12 weeks in long-term follow-up. The median survival follow-up time was 23.5 months (range 1.7 - 76.6 months)

Outcome measures

Outcome measures
Measure	Ramucirumab + Somatostatin Analog n=43 Participants Patients started treatment with ramucirumab at a dose of 8 mg/kg intravenously every 14 days of a 28-day treatment cycle. Patients already receiving a somatostatin analog continued somatostatin analog therapy at their current dose. Patients not already receiving a somatostatin analog initiated treatment at an approved dose, according to institutional guidelines.
Progression-Free Survival (PFS)	14.2 months Interval 9.0 to 25.6

SECONDARY outcome

Timeframe: The median survival follow-up time was 23.5 months (range 1.7 - 76.6 months)

To assess the overall survival duration of patients with advanced carcinoid tumors treated with ramucirumab. We will use the Kaplan-Meier method to estimate the distribution of overall survival.

Outcome measures

Outcome measures
Measure	Ramucirumab + Somatostatin Analog n=43 Participants Patients started treatment with ramucirumab at a dose of 8 mg/kg intravenously every 14 days of a 28-day treatment cycle. Patients already receiving a somatostatin analog continued somatostatin analog therapy at their current dose. Patients not already receiving a somatostatin analog initiated treatment at an approved dose, according to institutional guidelines.
Overall Survival	24.9 months Interval 20.7 to 43.1

SECONDARY outcome

Timeframe: 2 years

Population: Radiographic response rate was evaluated for all 43 eligible participants who started protocol therapy.

To evaluate disease response using RECIST criteria, version 1.1, of patients with advanced carcinoid tumors treated with Ramucirumab. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT include the following categories of disease response: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable disease (SD), less than 30% decrease but no more than 20% increase in sum of the longest diameter of target lesions. We will estimate the response rate and provide the associated 95% confidence interval.

Outcome measures

Outcome measures
Measure	Ramucirumab + Somatostatin Analog n=43 Participants Patients started treatment with ramucirumab at a dose of 8 mg/kg intravenously every 14 days of a 28-day treatment cycle. Patients already receiving a somatostatin analog continued somatostatin analog therapy at their current dose. Patients not already receiving a somatostatin analog initiated treatment at an approved dose, according to institutional guidelines.
Overall Radiographic Response Partial Response	2 Participants
Overall Radiographic Response Stable Disease	33 Participants
Overall Radiographic Response Progressive Disease	3 Participants
Overall Radiographic Response Not Restaged	5 Participants

SECONDARY outcome

Timeframe: 2 years

Population: 37 patients had an elevated chromogranin A level at baseline and were followed for biochemical response, as defined by a greater than 50% drop in chromogranin A level from baseline.

To evaluate biochemical response in patients with elevated chromogranin A at baseline, using levels of chromogranin-A measured at baseline and following treatment with Ramucirumab. Biochemical response was defined as greater than 50% drop in chromogranin A from baseline. During the screening period, all patients were evaluated for serum chromogranin A. Per protocol, if results of these are normal at baseline, they were not repeated while on study. If above institutional ULN at baseline, they were evaluated at time of tumor restaging.

Outcome measures

Outcome measures
Measure	Ramucirumab + Somatostatin Analog n=37 Participants Patients started treatment with ramucirumab at a dose of 8 mg/kg intravenously every 14 days of a 28-day treatment cycle. Patients already receiving a somatostatin analog continued somatostatin analog therapy at their current dose. Patients not already receiving a somatostatin analog initiated treatment at an approved dose, according to institutional guidelines.
Biochemical Response (Chromogranin A)	4 Participants

Adverse Events

Ramucirumab In Combination With Somatostatin Analog

Serious events: 15 serious events

Other events: 43 other events

Deaths: 33 deaths

Serious adverse events

Serious adverse events
Measure	Ramucirumab In Combination With Somatostatin Analog n=43 participants at risk Patients started treatment with ramucirumab at a dose of 8 mg/kg intravenously every 14 days of a 28-day treatment cycle. Patients already receiving a somatostatin analog continued somatostatin analog therapy at their current dose. Patients not already receiving a somatostatin analog initiated treatment at an approved dose, according to institutional guidelines.
Infections and infestations Pneumonia	7.0% 3/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Acute kidney injury	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Cardiac chest pain	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Clostridium difficile infection	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Colonic obstruction	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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.
Injury, poisoning and procedural complications Fall	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Intraventricular conduction	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Lower extremity edema	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Obstipation	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	7.0% 3/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Pharyngeal dysphagia	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Sepsis	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Small bowel obstruction	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Urinary tract infection	2.3% 1/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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

Other adverse events
Measure	Ramucirumab In Combination With Somatostatin Analog n=43 participants at risk Patients started treatment with ramucirumab at a dose of 8 mg/kg intravenously every 14 days of a 28-day treatment cycle. Patients already receiving a somatostatin analog continued somatostatin analog therapy at their current dose. Patients not already receiving a somatostatin analog initiated treatment at an approved dose, according to institutional guidelines.
Gastrointestinal disorders Abdominal pain	46.5% 20/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	27.9% 12/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	41.9% 18/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Anemia	25.6% 11/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	27.9% 12/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	60.5% 26/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	20.9% 9/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Bloating	7.0% 3/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	11.6% 5/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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.
Injury, poisoning and procedural complications Bruising	7.0% 3/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	14.0% 6/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	25.6% 11/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	32.6% 14/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	23.3% 10/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	53.5% 23/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	23.3% 10/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	7.0% 3/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	7.0% 3/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	32.6% 14/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	53.5% 23/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	34.9% 15/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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.
Injury, poisoning and procedural complications Fall	7.0% 3/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	83.7% 36/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Flushing	14.0% 6/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Gastroesophageal reflux disease	9.3% 4/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	14.0% 6/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	41.9% 18/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	23.3% 10/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Hoarseness	9.3% 4/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	23.3% 10/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	51.2% 22/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	11.6% 5/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	83.7% 36/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	39.5% 17/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	20.9% 9/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Hypoglycemia	14.0% 6/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	16.3% 7/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	20.9% 9/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	27.9% 12/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Hypophosphatemia	11.6% 5/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	9.3% 4/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	9.3% 4/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	7.0% 3/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	14.0% 6/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	39.5% 17/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	18.6% 8/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	9.3% 4/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	16.3% 7/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	16.3% 7/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	7.0% 3/43 • Number of events 6 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	46.5% 20/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	7.0% 3/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	60.5% 26/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Sinusitis	11.6% 5/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Sore throat	7.0% 3/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	9.3% 4/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Voice alteration	9.3% 4/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	20.9% 9/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	16.3% 7/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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	20.9% 9/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Lower extremity swelling	9.3% 4/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 cramping	7.0% 3/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Gum bleeding	9.3% 4/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Early satiety	7.0% 3/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Hip pain	9.3% 4/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Hemoglobin decreased	11.6% 5/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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 Post nasal drip	7.0% 3/43 • Adverse events evaluated on treatment on day 1 and 15 of each cycle and follow-up for 30 days off treatment. Observation period with median of 194 days and range (30-1416 days). All-Cause Mortality monitored/assessed up to 76.6 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

Dr. Jennifer Chan, MD

Dana-Farber Cancer Institute

Phone: 617-632-6315

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place