Trial Outcomes & Findings for Axitinib and Avelumab in Treating Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma (NCT NCT03990571)

NCT ID: NCT03990571

Last Updated: 2024-10-18

Results Overview

All eligible patients who received at least one cycle of treatment and had at least one restaging image were considered evaluable for the primary end point. Objective response includes complete response (CR) + partial response (PR). Radiographic imaging for tumor assessment was performed at baseline and then every 8 weeks.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 40 participants
• Primary outcome timeframe: Up to 33 months
• Results posted on: 2024-10-18

Participant Flow

40 participants enrolled from July 2019 to June 2021 (6 were screen failures).

Forty patients were enrolled from July 2019 to June 2021. Six were screen failures and thirty-four were treated.

Participant milestones

Measure	Treatment (Axitinib, Avelumab) Axitinib was administered orally at 5 mg twice a day, and avelumab was administered intravenously at 10 mg/Kg on days 1 and 15 of 28-day cycles
Overall Study STARTED	34
Overall Study COMPLETED	28
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Measure	Treatment (Axitinib, Avelumab) Axitinib was administered orally at 5 mg twice a day, and avelumab was administered intravenously at 10 mg/Kg on days 1 and 15 of 28-day cycles
Overall Study Withdrawal by Subject	1
Overall Study Insurance Issues	3
Overall Study Covid Restrictions	2

Baseline Characteristics

34 were treated and 6 of the 34 were evaluable for safety only and did not undergo the first re-staging imaging assessmen

Baseline characteristics by cohort

Measure	Treatment (Axitinib, Avelumab) n=34 Participants Axitinib was administered orally at 5 mg twice a day, and avelumab was administered intravenously at 10 mg/Kg on days 1 and 15 of 28-day cycles
Age, Categorical <=18 years	0 Participants n=34 Participants
Age, Categorical Between 18 and 65 years	27 Participants n=34 Participants
Age, Categorical >=65 years	7 Participants n=34 Participants
Age, Continuous	58 years n=34 Participants
Sex: Female, Male Female	16 Participants n=28 Participants • 34 were treated and 6 of the 34 were evaluable for safety only and did not undergo the first re-staging imaging assessmen
Sex: Female, Male Male	12 Participants n=28 Participants • 34 were treated and 6 of the 34 were evaluable for safety only and did not undergo the first re-staging imaging assessmen
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=28 Participants • 34 were treated and 6 of the 34 were evaluable for safety only and did not undergo the first re-staging imaging assessmen
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=28 Participants • 34 were treated and 6 of the 34 were evaluable for safety only and did not undergo the first re-staging imaging assessmen
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=28 Participants • 34 were treated and 6 of the 34 were evaluable for safety only and did not undergo the first re-staging imaging assessmen
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=28 Participants • 34 were treated and 6 of the 34 were evaluable for safety only and did not undergo the first re-staging imaging assessmen
Race (NIH/OMB) Asian	0 Participants n=28 Participants • 34 were treated and 6 of the 34 were evaluable for safety only and did not undergo the first re-staging imaging assessmen
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=28 Participants • 34 were treated and 6 of the 34 were evaluable for safety only and did not undergo the first re-staging imaging assessmen
Race (NIH/OMB) Black or African American	7 Participants n=28 Participants • 34 were treated and 6 of the 34 were evaluable for safety only and did not undergo the first re-staging imaging assessmen
Race (NIH/OMB) White	16 Participants n=28 Participants • 34 were treated and 6 of the 34 were evaluable for safety only and did not undergo the first re-staging imaging assessmen
Race (NIH/OMB) More than one race	5 Participants n=28 Participants • 34 were treated and 6 of the 34 were evaluable for safety only and did not undergo the first re-staging imaging assessmen
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=28 Participants • 34 were treated and 6 of the 34 were evaluable for safety only and did not undergo the first re-staging imaging assessmen
Region of Enrollment United States	28 participants n=34 Participants

PRIMARY outcome

Timeframe: Up to 33 months

Population: 40 participants enrolled from July 2019 to June 2021 (6 were screen failures), 34 were treated and 6 of the 34 were evaluable for safety only and did not undergo the first re-staging imaging assessment.

All eligible patients who received at least one cycle of treatment and had at least one restaging image were considered evaluable for the primary end point. Objective response includes complete response (CR) + partial response (PR). Radiographic imaging for tumor assessment was performed at baseline and then every 8 weeks.

Outcome measures

Measure	Treatment (Axitinib, Avelumab) n=28 Participants Axitinib was administered orally at 5 mg twice a day, and avelumab was administered intravenously at 10 mg/Kg on days 1 and 15 of 28-day cycles
Assess the Objective Response Rate (ORR) to Axitinib and Avelumab Combination According to RECIST 1.1 Criteria.	18 percentage of participants Interval 6.1 to 36.9

SECONDARY outcome

Timeframe: up to 40 months

Population: Forty patients enrolled from July 2019 to June 2021 (6 were screen failures), 34 were treated and 6 of the 34 were evaluable for safety only and did not undergo any re-staging imaging assessment, 28 were evaluable for time-to-event outcomes.

Progression-free survival (PFS) was defined as the duration from start of treatment to date of progression or death, whichever occurred first. Overall survival (OS) was defined as the duration from start of treatment to death. The Kaplan-Meier approach was used to estimate the PFS and OS distributions, along with median estimates with 95% CI.

Outcome measures

Measure	Treatment (Axitinib, Avelumab) n=28 Participants Axitinib was administered orally at 5 mg twice a day, and avelumab was administered intravenously at 10 mg/Kg on days 1 and 15 of 28-day cycles
Estimate Median Progression-free Survival, Median Overall Survival PFS	7.3 months Interval 3.7 to 11.2
Estimate Median Progression-free Survival, Median Overall Survival OS	16.6 months Interval 12.4 to Value not reached.

SECONDARY outcome

Timeframe: completed at 6 months from start of treatment

Population: Forty patients enrolled from July 2019 to June 2021 (6 were screen failures), 34 were treated and 6 of the 34 were evaluable for safety only and did not undergo any re-staging imaging assessment, 28 were evaluable for time-to-event outcomes.

Progression-free survival (PFS) was defined as the duration from start of treatment to date of progression or death, whichever occurred first. The PFS rate at 6-month was the percentage of patients without disease progression at 6 months. Overall survival (OS) was defined as the duration from start of treatment to death. The OS rate at 6-month was the percentage of living patients at 6 months. The Kaplan-Meier approach was used to estimate the PFS and OS distributions, along with median estimates with 95% CI.

Outcome measures

Measure	Treatment (Axitinib, Avelumab) n=28 Participants Axitinib was administered orally at 5 mg twice a day, and avelumab was administered intravenously at 10 mg/Kg on days 1 and 15 of 28-day cycles
Estimate Progression Free Survival Rate at 6 Months After Start of Treatment, Overall Survival Rate 6 Months After Start of Treatment PFS rate at 6-month	57 percentage of participants Interval 41.5 to 78.8
Estimate Progression Free Survival Rate at 6 Months After Start of Treatment, Overall Survival Rate 6 Months After Start of Treatment OS rate at 6-month	86 percentage of participants Interval 73.7 to 99.7

SECONDARY outcome

Timeframe: Up to 30 months

Population: Forty patients enrolled from July 2019 to June 2021 (6 were screen failures), 34 were treated and 6 of the 34 were evaluable for safety only and did not undergo any re-staging imaging assessment, 28 were evaluable for objective response and time-to-event outcomes. Five patients achieved confirmed partial response.

Duration of response (DoR) was measured from the date response criteria were met until the first date that progression was documented. The Kaplan-Meier approach was used to estimate the DOR distributions, along with median estimates with 95% CI.

Outcome measures

Measure	Treatment (Axitinib, Avelumab) n=5 Participants Axitinib was administered orally at 5 mg twice a day, and avelumab was administered intravenously at 10 mg/Kg on days 1 and 15 of 28-day cycles
Estimate Duration of Response	11 months Interval 5.5 to Value not reached.

SECONDARY outcome

Timeframe: Up to 30 months

Evaluated for the number of incidences for safety and toxicity for treatment related adverse events that occurred in > 10% of patients and all grade 3 or higher treatment related adverse events.

Outcome measures

Measure	Treatment (Axitinib, Avelumab) n=34 Participants Axitinib was administered orally at 5 mg twice a day, and avelumab was administered intravenously at 10 mg/Kg on days 1 and 15 of 28-day cycles
Evaluate Safety and Toxicity Adverse Events	34 Participants
Evaluate Safety and Toxicity Serious Adverse Events	7 Participants
Evaluate Safety and Toxicity Labs	19 Participants
Evaluate Safety and Toxicity Deaths	1 Participants

Adverse Events

Treatment (Axitinib, Avelumab)

Serious events: 7 serious events

Other events: 31 other events

Deaths: 1 deaths

Serious adverse events

Measure	Treatment (Axitinib, Avelumab) n=34 participants at risk Axitinib was administered orally at 5 mg twice a day, and avelumab was administered intravenously at 10 mg/Kg on days 1 and 15 of 28-day cycles
Vascular disorders Deep Vein Thrombosis	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Investigations Transaminitis	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Respiratory, thoracic and mediastinal disorders SOB	5.9% 2/34 • Number of events 2 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Respiratory, thoracic and mediastinal disorders Coughing	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Respiratory, thoracic and mediastinal disorders Pneumonia	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) neoplasm pain	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Cardiac disorders Chest pain	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.

Other adverse events

Measure	Treatment (Axitinib, Avelumab) n=34 participants at risk Axitinib was administered orally at 5 mg twice a day, and avelumab was administered intravenously at 10 mg/Kg on days 1 and 15 of 28-day cycles
Gastrointestinal disorders Abdominal pain	5.9% 2/34 • Number of events 2 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Investigations Alanine aminotransferase increased	14.7% 5/34 • Number of events 8 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Investigations Alkaline phosphatase increased	5.9% 2/34 • Number of events 3 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Investigations Allergic reaction	5.9% 2/34 • Number of events 2 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Investigations Anemia	11.8% 4/34 • Number of events 6 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Investigations Anorexia	20.6% 7/34 • Number of events 8 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Investigations Anxiety	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Investigations Arthralgia	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Musculoskeletal and connective tissue disorders Arthritis	2.9% 1/34 • Number of events 2 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Investigations Aspartate aminotransferase increased	14.7% 5/34 • Number of events 5 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Musculoskeletal and connective tissue disorders Back pain	8.8% 3/34 • Number of events 3 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Eye disorders Blurred vision	5.9% 2/34 • Number of events 2 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Musculoskeletal and connective tissue disorders Bone pain	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Cardiac disorders Chest pain - cardiac	8.8% 3/34 • Number of events 3 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Musculoskeletal and connective tissue disorders Chest wall pain	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Gastrointestinal disorders Constipation	20.6% 7/34 • Number of events 8 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Respiratory, thoracic and mediastinal disorders Cough	20.6% 7/34 • Number of events 7 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Investigations Creatinine increased	8.8% 3/34 • Number of events 5 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Gastrointestinal disorders Diarrhea	35.3% 12/34 • Number of events 21 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Nervous system disorders Dizziness	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Gastrointestinal disorders Dry mouth	8.8% 3/34 • Number of events 3 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Skin and subcutaneous tissue disorders Dry skin	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Nervous system disorders Dysesthesia	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Nervous system disorders Dysgeusia	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Gastrointestinal disorders Dysphagia	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Respiratory, thoracic and mediastinal disorders Dyspnea	26.5% 9/34 • Number of events 10 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, specify (Earache B/L)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Ear and labyrinth disorders Ear pain	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Endocrine disorders Endocrine disorders - Other, specify (Low cortisol levels)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Respiratory, thoracic and mediastinal disorders Epistaxis	17.6% 6/34 • Number of events 6 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Eye disorders Eye disorders - Other, specify (right eye fasciculations)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Eye disorders Eye disorders - Other, specify (diplopia)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Eye disorders Eye disorders - Other, specify (Left eye droop)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Eye disorders Eye disorders - Other, specify (Loss of vision (both eyes))	2.9% 1/34 • Number of events 2 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Eye disorders Eye pain	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Injury, poisoning and procedural complications Fall	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
General disorders Fatigue	64.7% 22/34 • Number of events 32 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Eye disorders Floaters (Vision floaters (left is greater than right))	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
General disorders Fever	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
General disorders Gait disturbance	8.8% 3/34 • Number of events 3 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Gastrointestinal disorders Gastroesophageal reflux disease	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify (C. diff)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify (Epigastric)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify (Gastric pain)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify (hematochezia)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify (Stomach infection)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify (stomatitis)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify (Thick saliva)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
General disorders General disorders and administration site conditions - Other, specify (Left leg weakness)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
General disorders General disorders and administration site conditions - Other, specify (Asthenia)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Psychiatric disorders Hallucinations	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Nervous system disorders Headache	14.7% 5/34 • Number of events 5 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Hepatobiliary disorders Hepatobiliary disorders - Other, specify (Deep Vein Thrombosis left arm)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Hepatobiliary disorders HiccupsHiccups	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Respiratory, thoracic and mediastinal disorders Hiccups	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Respiratory, thoracic and mediastinal disorders Hoarseness	20.6% 7/34 • Number of events 10 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Metabolism and nutrition disorders Hypercalcemia	14.7% 5/34 • Number of events 5 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Metabolism and nutrition disorders Hyperkalemia	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Metabolism and nutrition disorders Hypermagnesemia	5.9% 2/34 • Number of events 2 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Vascular disorders Hypertension	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Endocrine disorders Hyperthyroidism	5.9% 2/34 • Number of events 2 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Metabolism and nutrition disorders Hypokalemia	5.9% 2/34 • Number of events 2 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Metabolism and nutrition disorders Hypomagnesemia	5.9% 2/34 • Number of events 2 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Metabolism and nutrition disorders Hyponatremia	8.8% 3/34 • Number of events 3 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Vascular disorders Hypotension	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Endocrine disorders Hypothyroidism	14.7% 5/34 • Number of events 5 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
General disorders Infusion related reaction	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, specify (Left ear bleeding (intermittent))	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Psychiatric disorders Insomnia	5.9% 2/34 • Number of events 2 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Investigations Investigations - Other, specify (Transaminitis)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Reproductive system and breast disorders Irregular menstruation	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Investigations Lymphocyte count decreased	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Gastrointestinal disorders Mucositis oral	29.4% 10/34 • Number of events 10 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify (bilateral lower extremity muscle a	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify (Cramping hands and feet)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify (Hip pain)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify (Left shoulder blade)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify (leg pain)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify (Muscle ache 4th-5th right rib)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify (Shoulder Pain)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify (Swollen left knuckle)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify (Left shoulder pain)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify (Abdominal pain)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Gastrointestinal disorders Nausea	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Nervous system disorders Nervous system disorders - Other, specify (Restless legs)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Nervous system disorders Nervous system disorders - Other, specify (neuropathic)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Investigations Neutrophil count decreased	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Gastrointestinal disorders Oral pain (Sore mouth)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Gastrointestinal disorders Oral pain	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
General disorders Pain	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	17.6% 6/34 • Number of events 12 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Infections and infestations Papulopustular rash	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Nervous system disorders Paresthesia	8.8% 3/34 • Number of events 3 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Respiratory, thoracic and mediastinal disorders Pharyngeal mucositis	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Investigations Platelet count decreased	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.9% 2/34 • Number of events 2 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Hepatobiliary disorders Portal vein thrombosis (deep vein thrombosis)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Respiratory, thoracic and mediastinal disorders Productive cough	5.9% 2/34 • Number of events 2 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Skin and subcutaneous tissue disorders Pruritus	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Skin and subcutaneous tissue disorders Rash maculo-papular	8.8% 3/34 • Number of events 3 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify (Bronchitis)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify (Runny nose)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify (Sinus infection)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Infections and infestations Sinusitis	5.9% 2/34 • Number of events 2 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify (Itchy skin)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify (Lip ulcer)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify (Pruritic rash)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Respiratory, thoracic and mediastinal disorders Sore throat	8.8% 3/34 • Number of events 3 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Surgical and medical procedures Surgical and medical procedures - Other, specify (Colonoscopy)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Surgical and medical procedures Surgical and medical procedures - Other, specify (Repair of reducible inguinal hernia)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Surgical and medical procedures Surgical and medical procedures - Other, specify (Thoracentesis)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Gastrointestinal disorders Toothache	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Renal and urinary disorders Urinary incontinence	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Eye disorders Uveitis	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Vascular disorders Vascular disorders - Other, specify (Ecchymosis)	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Respiratory, thoracic and mediastinal disorders Voice alteration	2.9% 1/34 • Number of events 1 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Gastrointestinal disorders Vomiting	8.8% 3/34 • Number of events 3 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.
Investigations Weight loss	26.5% 9/34 • Number of events 12 • Adverse Events monitored/assessed up to 30 months, All- Cause Mortality monitored/assessed up to 40 months. Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion. All eligible participants who received at least one cycle of treatment were considered evaluable for safety analyses. AEs (related and unrelated) were graded according to Common Terminology Criteria for AEs version 4.0.

Additional Information

Dr. Renata Ferrarotto

The University of Texas M D Anderson Cancer Center

Phone: (713) 745-6774

Email: rferrarotto@mdanderson.org

Results disclosure agreements

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