Trial Outcomes & Findings for Cabozantinib for Metastatic Triple Negative BrCa (NCT NCT01738438)

Last Updated: 2016-12-06

Results Overview

The objective response rate (ORR) was defined as achieving complete response (CR) or partial response (PR) on treatment based on RECIST1.1 criteria. For target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. Confirmatory scans were required 3 weeks following initial documentation.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

Disease was evaluated radiologically at baseline, week 6 and every 9 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 3 cycles range (1-17).

Results posted on

2016-12-06

Participant Flow

Patients enrolled from January 2013 through June 2014.

Participant milestones

Participant milestones
Measure	Cabozantinib Cabozantinib was given at a dose of 60 mg orally once per day for 21 day cycles. Treatment continued in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	35
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	35

Reasons for withdrawal

Reasons for withdrawal
Measure	Cabozantinib Cabozantinib was given at a dose of 60 mg orally once per day for 21 day cycles. Treatment continued in the absence of disease progression or unacceptable toxicity.
Overall Study Disease Progression	32
Overall Study Adverse Event	3

Baseline Characteristics

Cabozantinib for Metastatic Triple Negative BrCa

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cabozantinib n=35 Participants Cabozantinib was given at a dose of 60 mg orally once per day for 21 day cycles. Treatment continued in the absence of disease progression or unacceptable toxicity.
Age, Continuous	50 years n=5 Participants
Gender Female	35 Participants n=5 Participants
Gender Male	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	32 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	35 participants n=5 Participants

PRIMARY outcome

Timeframe: Disease was evaluated radiologically at baseline, week 6 and every 9 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 3 cycles range (1-17).

Population: The analysis dataset is comprised of all treated patients.

Outcome measures

Outcome measures
Measure	Cabozantinib n=35 Participants Cabozantinib was given at a dose of 60 mg orally once per day for 21 day cycles. Treatment continued in the absence of disease progression or unacceptable toxicity.
Objective Response Rate	0.09 proportion of participants Interval 0.02 to 0.26

SECONDARY outcome

Population: The analysis dataset is comprised of all treated patients.

Progression-free survival (PFS) estimated using Kaplan-Meier methods was defined as the time from registration to documented disease progression (PD) or death. Based on RECIST1.1, radiographic PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum since beginning therapy, the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Patients who were event-free were censored at the date of their last disease evaluation.

Outcome measures

Outcome measures
Measure	Cabozantinib n=35 Participants Cabozantinib was given at a dose of 60 mg orally once per day for 21 day cycles. Treatment continued in the absence of disease progression or unacceptable toxicity.
Progression Free Survival	2 months Interval 1.3 to 3.3

POST_HOC outcome

Timeframe: Disease was evaluated radiologically at baseline, week 6 and week 15 on treatment.

Population: The analysis dataset is comprised of all treated patients.

The 15-week clinical benefit rate (CBR) was defined as absence of disease progression (PD) per RECIST1.1 criteria at the second disease assessment (week 15). Radiographic PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum since beginning therapy, the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Confirmatory scans for response were required 3 weeks following initial documentation.

Outcome measures

Outcome measures
Measure	Cabozantinib n=35 Participants Cabozantinib was given at a dose of 60 mg orally once per day for 21 day cycles. Treatment continued in the absence of disease progression or unacceptable toxicity.
15-Week Clinical Benefit Rate	.34 proportion of participants Interval 0.19 to 0.52

Adverse Events

Cabozantinib

Serious events: 14 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cabozantinib n=35 participants at risk Cabozantinib was given at a dose of 60 mg orally once per day for 21 day cycles. Treatment continued in the absence of disease progression or unacceptable toxicity.
Infections and infestations Infections and infestations - Other	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Injury, poisoning and procedural complications Wound dehiscence	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Investigations Activated partial thromboplastin time prolonged	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Investigations Alanine aminotransferase increased	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Investigations Aspartate aminotransferase increased	5.7% 2/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Investigations Lipase increased	8.6% 3/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Metabolism and nutrition disorders Hypophosphatemia	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Musculoskeletal and connective tissue disorders Bone pain	5.7% 2/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Vascular disorders Hypertension	5.7% 2/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Vascular disorders Thromboembolic event	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.

Other adverse events

Other adverse events
Measure	Cabozantinib n=35 participants at risk Cabozantinib was given at a dose of 60 mg orally once per day for 21 day cycles. Treatment continued in the absence of disease progression or unacceptable toxicity.
Investigations Blood bilirubin increased	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Investigations Lymphocyte count decreased	5.7% 2/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Investigations Neutrophil count decreased	5.7% 2/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Investigations Platelet count decreased	8.6% 3/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Investigations Serum amylase increased	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Investigations White blood cell decreased	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Blood and lymphatic system disorders Anemia	5.7% 2/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Blood and lymphatic system disorders Disseminated intravascular coagulation	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Endocrine disorders Hyperthyroidism	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Endocrine disorders Hypothyroidism	17.1% 6/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Eye disorders Eyelid function disorder	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Gastrointestinal disorders Abdominal pain	5.7% 2/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Gastrointestinal disorders Diarrhea	40.0% 14/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Gastrointestinal disorders Dry mouth	5.7% 2/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Gastrointestinal disorders Dyspepsia	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Gastrointestinal disorders Flatulence	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Gastrointestinal disorders Gastroesophageal reflux disease	11.4% 4/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Gastrointestinal disorders Mucositis oral	37.1% 13/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Gastrointestinal disorders Nausea	28.6% 10/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Gastrointestinal disorders Toothache	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Gastrointestinal disorders Vomiting	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Gastrointestinal disorders Gastrointestinal disorders - Other	54.3% 19/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
General disorders Fatigue	74.3% 26/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
General disorders Malaise	5.7% 2/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Infections and infestations Mucosal infection	5.7% 2/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Injury, poisoning and procedural complications Wound dehiscence	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Investigations Alanine aminotransferase increased	14.3% 5/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Investigations Alkaline phosphatase increased	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Investigations Aspartate aminotransferase increased	25.7% 9/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Investigations Investigations - Other	11.4% 4/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Metabolism and nutrition disorders Anorexia	34.3% 12/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Metabolism and nutrition disorders Hyperglycemia	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Metabolism and nutrition disorders Hypomagnesemia	5.7% 2/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Metabolism and nutrition disorders Hypophosphatemia	5.7% 2/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Musculoskeletal and connective tissue disorders Back pain	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Musculoskeletal and connective tissue disorders Pain in extremity	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	8.6% 3/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Nervous system disorders Dysgeusia	20.0% 7/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Nervous system disorders Headache	5.7% 2/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Psychiatric disorders Anxiety	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Psychiatric disorders Confusion	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Psychiatric disorders Psychiatric disorders - Other	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Renal and urinary disorders Proteinuria	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Reproductive system and breast disorders Irregular menstruation	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Respiratory, thoracic and mediastinal disorders Dyspnea	5.7% 2/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Respiratory, thoracic and mediastinal disorders Hoarseness	17.1% 6/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Respiratory, thoracic and mediastinal disorders Voice alteration	8.6% 3/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Skin and subcutaneous tissue disorders Nail loss	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	34.3% 12/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Skin and subcutaneous tissue disorders Pruritus	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Skin and subcutaneous tissue disorders Rash acneiform	5.7% 2/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Skin and subcutaneous tissue disorders Rash maculo-papular	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Skin and subcutaneous tissue disorders Skin hypopigmentation	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Vascular disorders Hypertension	20.0% 7/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.
Vascular disorders Thromboembolic event	2.9% 1/35 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17). Maximum grade toxicity by type for a patient over time including only events with possible, probable or definite attribution was first calculated. Patients appear once for a given toxicity type. Serious and Other AEs were defined as events of grades 3-5 and grades1-2, respectively, based on CTCAEv3. 'Other' events have no further specification.

Additional Information

Sara Tolaney, MD

Dana-Farber Cancer Institute

Phone: 617.632.2335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place