Trial Outcomes & Findings for Study of Vandetanib Combined With Chemotherapy to Treat Advanced Non-small Cell Lung Cancer (NCT NCT00687297)

Last Updated: 2018-05-30

Results Overview

Time from randomization (prior to induction) to first evidence of disease progression or death without progression. Participants alive without progression were censored at the date of last disease evaluation.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

162 participants

Primary outcome timeframe

Assessed every 2 cycles (1 cycle = 3 weeks during induction and 4 weeks during maintenance))

Results posted on

2018-05-30

Participant Flow

Participant milestones

Participant milestones
Measure	Randomized to Vandetanib Maintenance Docetaxel (75mg/m2)IV (in the vein) + Carboplatin IV (AUC=6) day 1 of 21 day cycle + vandetanib (100mg) days 1 through 21 (daily) x 4 cycles. If SD, PR CR after 4 cycles --\> Maintenance treatment: vandetanib (300mg) daily until progression \[1 Cycle= 28 days\]	Randomized to Placebo Maintenance Docetaxel (75mg/m2)IV (in the vein) + Carboplatin IV (AUC=6) day 1 of 21 day cycle + vandetanib (100mg) days 1 through 21 (daily) x 4 cycles. If SD, PR CR after 4 cycles --\> Maintenance treatment: Placebo 3 tablets daily until progression \[1 Cycle= 28 days\]
Randomization STARTED	80	82
Randomization COMPLETED	77	81
Randomization NOT COMPLETED	3	1
Induction STARTED	77	81
Induction COMPLETED	32	26
Induction NOT COMPLETED	45	55
Maintenance STARTED	32	26
Maintenance COMPLETED	29	25
Maintenance NOT COMPLETED	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Randomized to Vandetanib Maintenance Docetaxel (75mg/m2)IV (in the vein) + Carboplatin IV (AUC=6) day 1 of 21 day cycle + vandetanib (100mg) days 1 through 21 (daily) x 4 cycles. If SD, PR CR after 4 cycles --\> Maintenance treatment: vandetanib (300mg) daily until progression \[1 Cycle= 28 days\]	Randomized to Placebo Maintenance Docetaxel (75mg/m2)IV (in the vein) + Carboplatin IV (AUC=6) day 1 of 21 day cycle + vandetanib (100mg) days 1 through 21 (daily) x 4 cycles. If SD, PR CR after 4 cycles --\> Maintenance treatment: Placebo 3 tablets daily until progression \[1 Cycle= 28 days\]
Randomization Withdrawal by Subject	2	0
Randomization Withdrew before treatment, ineligible	1	1
Induction Withdrawal by Subject	4	4
Induction Adverse Event	16	15
Induction Death	7	11
Induction Lack of Efficacy	17	21
Induction Ineligible	0	1
Induction Patient Noncompliance	1	0
Induction Physician Decision	0	2
Induction Other	0	1

Baseline Characteristics

Study of Vandetanib Combined With Chemotherapy to Treat Advanced Non-small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Randomized to Vandetanib Maintenance n=80 Participants Docetaxel (75mg/m2)IV (in the vein) + Carboplatin IV (AUC=6) day 1 of 21 day cycle + vandetanib (100mg) days 1 through 21 (daily) x 4 cycles. If SD, PR CR after 4 cycles --\> Maintenance treatment: vandetanib (300mg) daily until progression \[1 Cycle= 28 days\]	Randomized to Placebo Maintenance n=82 Participants Docetaxel (75mg/m2)IV (in the vein) + Carboplatin IV (AUC=6) day 1 of 21 day cycle + vandetanib (100mg) days 1 through 21 (daily) x 4 cycles. If SD, PR CR after 4 cycles --\> Maintenance treatment: Placebo 3 tablets daily until progression \[1 Cycle= 28 days\]	Total n=162 Participants Total of all reporting groups
Age, Continuous	63.5 years n=5 Participants	63 years n=7 Participants	63 years n=5 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	40 Participants n=7 Participants	78 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	42 Participants n=7 Participants	84 Participants n=5 Participants
Region of Enrollment United States	80 participants n=5 Participants	82 participants n=7 Participants	162 participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed every 2 cycles (1 cycle = 3 weeks during induction and 4 weeks during maintenance))

Population: All randomized patients were included.

Outcome measures

Outcome measures
Measure	All Randomized Patients n=162 Participants All patients enrolled in the study	Randomized to Placebo Maintenance Docetaxel (75mg/m2)IV (in the vein) + Carboplatin IV (AUC=6) day 1 of 21 day cycle + vandetanib (100mg) days 1 through 21 (daily) x 4 cycles. If SD, PR CR after 4 cycles --\> Maintenance treatment: Placebo 3 tablets daily until progression \[1 Cycle= 28 days\]
Progression-free Survival	4.5 Months Interval 3.6 to 4.9	—

SECONDARY outcome

Timeframe: Assessed every 2 cycles (1 cycle = 3 weeks during induction and 4 weeks during maintenance))

Population: All randomized patients were included.

Best overall response (complete or partial response), assessed using RECIST criteria (version 1.0)

Outcome measures

Outcome measures
Measure	All Randomized Patients n=82 Participants All patients enrolled in the study	Randomized to Placebo Maintenance n=80 Participants Docetaxel (75mg/m2)IV (in the vein) + Carboplatin IV (AUC=6) day 1 of 21 day cycle + vandetanib (100mg) days 1 through 21 (daily) x 4 cycles. If SD, PR CR after 4 cycles --\> Maintenance treatment: Placebo 3 tablets daily until progression \[1 Cycle= 28 days\]
Objective Response Rate	18.8 percentage of participants Interval 10.9 to 29.0	18.3 percentage of participants Interval 10.6 to 28.4

SECONDARY outcome

Timeframe: every 2 cycles (every 6 weeks during induction, every 8 weeks during maintenance)

Population: All randomized patients were included.

Time from randomization to first evidence of disease progression or death. Patients alive without progression are censored at the date of last disease evaluation.

Outcome measures

Outcome measures
Measure	All Randomized Patients n=80 Participants All patients enrolled in the study	Randomized to Placebo Maintenance n=82 Participants Docetaxel (75mg/m2)IV (in the vein) + Carboplatin IV (AUC=6) day 1 of 21 day cycle + vandetanib (100mg) days 1 through 21 (daily) x 4 cycles. If SD, PR CR after 4 cycles --\> Maintenance treatment: Placebo 3 tablets daily until progression \[1 Cycle= 28 days\]
Progression-free Survival	4.5 months Interval 3.3 to 5.8	4.2 months Interval 2.8 to 4.9

Adverse Events

Treated on Vandetanib Maintenance

Serious events: 22 serious events

Other events: 29 other events

Deaths: 0 deaths

Treated on Placebo Maintenance

Serious events: 11 serious events

Other events: 22 other events

Deaths: 0 deaths

All Treated Patients - Induction

Serious events: 111 serious events

Other events: 145 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Statistician

PrECOG

Phone: 617-632-3633

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Treated on Vandetanib Maintenance n=32 participants at risk Adverse events among patients receiving Vandetanib using the maintenance phase of the study	Treated on Placebo Maintenance n=26 participants at risk Adverse events among patients receiving placebo during the maintenance phase of the study	All Treated Patients - Induction n=157 participants at risk Adverse events occurring during induction among all treated patients
Immune system disorders Allergic Reaction	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	1.9% 3/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Gastrointestinal disorders Anorexia	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	1.9% 3/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Psychiatric disorders Anxiety	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Cardiac disorders Atrial fibrillation	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Musculoskeletal and connective tissue disorders Back pain	3.1% 1/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	7.7% 2/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Nervous system disorders CNS cerebrovascular ischemia	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	1.3% 2/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Cardiac disorders Cardiac - other	3.1% 1/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Gastrointestinal disorders Colitis, infectious	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
General disorders Death NOS	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Metabolism and nutrition disorders Dehydration	3.1% 1/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.2% 5/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Psychiatric disorders Depression	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Gastrointestinal disorders Diarrhea w/o Prior Colostomy	9.4% 3/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	8.9% 14/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Nervous system disorders Dizziness	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Skin and subcutaneous tissue disorders Dry Skin	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Respiratory, thoracic and mediastinal disorders Dyspnea	9.4% 3/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 1/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	1.9% 3/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Skin and subcutaneous tissue disorders Erythema multiforme	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Musculoskeletal and connective tissue disorders Extremity - limb, pain	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
General disorders Fatigue	6.2% 2/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 1/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	7.6% 12/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Blood and lymphatic system disorders Febrile Neutropenia	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	6.4% 10/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Blood and lymphatic system disorders Anemia	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	7.7% 2/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	2.5% 4/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Respiratory, thoracic and mediastinal disorders Hemorrhage - other	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Metabolism and nutrition disorders Hyperglycemia	3.1% 1/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Vascular disorders Hypertension	6.2% 2/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	1.9% 3/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	1.9% 3/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Metabolism and nutrition disorders Hypokalemia	3.1% 1/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	2.5% 4/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	1.3% 2/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Metabolism and nutrition disorders Hyponatremia	3.1% 1/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 1/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	2.5% 4/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Respiratory, thoracic and mediastinal disorders Hypoxia	3.1% 1/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Infections and infestations Infection w grade 3-4 neutrophils, lung	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	1.9% 3/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Infections and infestations Infection w/unk ANC, abdomen NOS	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Infections and infestations Infection w/unk ANC, liver	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Infections and infestations Infection w/unk ANC, lung	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 1/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	1.3% 2/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Infections and infestations Infection - other	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	1.9% 3/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
General disorders Insomnia	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Musculoskeletal and connective tissue disorders Joint pain	3.1% 1/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 1/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Blood and lymphatic system disorders Leukocytes increased	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	15.9% 25/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Respiratory, thoracic and mediastinal disorders Lung hemorrhage	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Investigations Lymphopenia	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.

Other adverse events
Measure	Treated on Vandetanib Maintenance n=32 participants at risk Adverse events among patients receiving Vandetanib using the maintenance phase of the study	Treated on Placebo Maintenance n=26 participants at risk Adverse events among patients receiving placebo during the maintenance phase of the study	All Treated Patients - Induction n=157 participants at risk Adverse events occurring during induction among all treated patients
Gastrointestinal disorders Abdomen, Pain	9.4% 3/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	4.5% 7/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Skin and subcutaneous tissue disorders Alopecia	25.0% 8/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	15.4% 4/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	31.8% 50/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Metabolism and nutrition disorders Anorexia	18.8% 6/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	11.5% 3/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	17.2% 27/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Musculoskeletal and connective tissue disorders Back, pain	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	7.7% 2/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.2% 5/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Gastrointestinal disorders Constipation	3.1% 1/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 1/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	10.8% 17/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Respiratory, thoracic and mediastinal disorders Cough	6.2% 2/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	11.5% 3/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 6/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Investigations Creatinine increased	9.4% 3/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 6/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Gastrointestinal disorders Diarrhea w/o prior colostomy	46.9% 15/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	11.5% 3/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	28.0% 44/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Nervous system disorders Dizziness	9.4% 3/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 1/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.2% 5/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Gastrointestinal disorders Dry Mouth	9.4% 3/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Skin and subcutaneous tissue disorders Dry Skin	12.5% 4/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	15.4% 4/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.2% 5/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Gastrointestinal disorders Dyspepsia	6.2% 2/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 1/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	7.0% 11/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Gastrointestinal disorders Dysphagia	6.2% 2/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 1/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	2.5% 4/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Respiratory, thoracic and mediastinal disorders Dyspnea	9.4% 3/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	11.5% 3/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.2% 5/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
General disorders Edema, head and neck	6.2% 2/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 1/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
General disorders Edema, limb	6.2% 2/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	5.7% 9/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
General disorders Fatigue	31.2% 10/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	38.5% 10/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	33.8% 53/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Blood and lymphatic system disorders Anemia	9.4% 3/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 1/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	14.6% 23/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Metabolism and nutrition disorders Hyperglycemia	3.1% 1/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	11.5% 3/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.2% 5/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Vascular disorders Hypertension	6.2% 2/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	7.7% 2/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	4.5% 7/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Metabolism and nutrition disorders Hypokalemia	6.2% 2/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	1.3% 2/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Metabolism and nutrition disorders Hypomagnesemia	9.4% 3/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	8.3% 13/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Musculoskeletal and connective tissue disorders Joint pain	6.2% 2/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 6/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Blood and lymphatic system disorders Leukopenia	6.2% 2/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	5.7% 9/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Gastrointestinal disorders Muco/stomatitis by exam, oral cavity	9.4% 3/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 1/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	17.2% 27/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Skin and subcutaneous tissue disorders Nail changes	6.2% 2/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	15.4% 4/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 6/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Gastrointestinal disorders Nausea	21.9% 7/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	15.4% 4/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	31.8% 50/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Nervous system disorders Neuropathy, sensory	15.6% 5/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	11.5% 3/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	14.0% 22/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Respiratory, thoracic and mediastinal disorders Nose, hemorrhage	6.2% 2/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	5.7% 9/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Investigations Platelet count decreased	0.00% 0/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	7.6% 12/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Skin and subcutaneous tissue disorders Photosensitivity	9.4% 3/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.64% 1/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Skin and subcutaneous tissue disorders Pruritus/itching	12.5% 4/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	7.7% 2/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 6/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Skin and subcutaneous tissue disorders Rash/desquamation	34.4% 11/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	19.2% 5/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	15.9% 25/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Skin and subcutaneous tissue disorders Rash: acne/acneiform	18.8% 6/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 1/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	2.5% 4/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
General disorders Rigors/chills	6.2% 2/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	3.8% 1/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	1.3% 2/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Nervous system disorders Taste disturbance	6.2% 2/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	8.9% 14/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Vascular disorders Thrombosis/thrombus/embolism	3.1% 1/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	5.1% 8/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Gastrointestinal disorders Vomiting	9.4% 3/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	14.0% 22/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.
Investigations Weight loss	6.2% 2/32 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	0.00% 0/26 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.	5.7% 9/157 • Adverse events were assessed every 3 weeks during induction and every 4 weeks during maintenance. Serious adverse events are defined as events of grade 3 or higher that were considered possibly, probably, or definitely treatment-related. Other adverse events include grade 1 or 2 events possibly, probably or definitely treatment-related occurring at a rate of 5% or higher.