Trial Outcomes & Findings for Eribulin With Trastuzumab as First-line Therapy for Locally Recurrent or Metastatic HER2 Positive Breast Cancer (NCT NCT01269346)

Last Updated: 2023-06-22

Results Overview

The Objective Response Rate (Complete Response plus Partial Response, (CR + PR)) was defined as the proportion of participants who have a best overall response of confirmed CR or PR based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the Investigator. Tumor assessment was by computed tomography (CT)/magnetic resonance imaging (MRI). To assess best response (CR, PR, stable disease (SD), progressive disease (PD), or not estimable (NE)), the Investigator selected up to five measurable target lesions (2 per organ). All other lesions were identified as nontarget lesions. Each participant's overall tumor burden at Baseline was compared with subsequent measurements of the target lesions. For participants with CR or PR, changes in tumor sizes had to be confirmed by repeat evaluations performed not fewer than four weeks after the initial response assessment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

52 participants

Primary outcome timeframe

Baseline (within 28 days of first infusion of study drug); Treatment Phase (every 6 weeks during the first 6 cycles); Extension Phase (every 12 weeks) to PR or CR

Results posted on

2023-06-22

Participant Flow

A total of 64 participants were screened for entry into the study, of these participants 12 were screen failures and 52 were enrolled into the study and received at least one dose of study treatment.

Participant milestones

Participant milestones
Measure	Eribulin Mesylate in Combination With Trastuzumab Eribulin Mesylate: Eribulin mesylate 1.4 mg/m\^2 was administered as an intravenous (IV) infusion (over 2 to 5 minutes) on Days 1 and 8 of each 3-week cycle. Trastuzumab 8 mg/kg was administered as an IV infusion over a 90-minute period on Day 1 of Cycle 1. Thereafter, trastuzumab 6 mg/kg was administered as an IV infusion over a 30-minute period on Day 1 of each subsequent 21-day cycle.
Treatment Phase STARTED	52
Treatment Phase Completed 6 Cycles	45
Treatment Phase COMPLETED	43
Treatment Phase NOT COMPLETED	9
Extension Phase STARTED	43
Extension Phase COMPLETED	0
Extension Phase NOT COMPLETED	43

Reasons for withdrawal

Reasons for withdrawal
Measure	Eribulin Mesylate in Combination With Trastuzumab Eribulin Mesylate: Eribulin mesylate 1.4 mg/m\^2 was administered as an intravenous (IV) infusion (over 2 to 5 minutes) on Days 1 and 8 of each 3-week cycle. Trastuzumab 8 mg/kg was administered as an IV infusion over a 90-minute period on Day 1 of Cycle 1. Thereafter, trastuzumab 6 mg/kg was administered as an IV infusion over a 30-minute period on Day 1 of each subsequent 21-day cycle.
Treatment Phase Disease progression	3
Treatment Phase Adverse Event	3
Treatment Phase Withdrawal by Subject	1
Treatment Phase Other	2
Extension Phase Adverse Event	6
Extension Phase Withdrawal by Subject	4
Extension Phase Disease progression	22
Extension Phase Physician decision or participant choice	9
Extension Phase Clinical progression	1
Extension Phase Started a prohibited con med	1

Baseline Characteristics

Eribulin With Trastuzumab as First-line Therapy for Locally Recurrent or Metastatic HER2 Positive Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Eribulin Mesylate in Combination With Trastuzumab n=52 Participants Eribulin Mesylate: Eribulin mesylate 1.4 mg/m\^2 was administered as an intravenous (IV) infusion (over 2 to 5 minutes) on Days 1 and 8 of each 3-week cycle. Trastuzumab 8 mg/kg was administered as in IV infusion over a 90-minute period on Day 1 of Cycle 1. Thereafter, trastuzumab 6 mg/kg was administered as an IV infusion over a 30-minute period on Day 1 of each subsequent 21-day cycle.
Age, Continuous	58.7 Years STANDARD_DEVIATION 10.92 • n=5 Participants
Sex: Female, Male Female	51 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (within 28 days of first infusion of study drug); Treatment Phase (every 6 weeks during the first 6 cycles); Extension Phase (every 12 weeks) to PR or CR

Population: FAS included all participants who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate in Combination With Trastuzumab n=52 Participants Eribulin Mesylate: Eribulin mesylate 1.4 mg/m\^2 was administered as an intravenous (IV) infusion (over 2 to 5 minutes) on Days 1 and 8 of each 3-week cycle. Trastuzumab 8 mg/kg was administered as in IV infusion over a 90-minute period on Day 1 of Cycle 1. Thereafter, trastuzumab 6 mg/kg was administered as an IV infusion over a 30-minute period on Day 1 of each subsequent 21-day cycle.
Objective Response Rate	71.2 Percentage of participants Interval 56.92 to 82.87

SECONDARY outcome

Timeframe: From date of first dose of study drug to the earliest date that CR or PR was objectively documented, assessed up to data cutoff (12 Sep 2013), up to approximately 2 years 9 months

Population: FAS included all participants who received at least one dose of study drug. Analyzed for responders (CR or PR) only.

Time to first response was defined for participants whose best overall response was a CR or PR.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate in Combination With Trastuzumab n=37 Participants Eribulin Mesylate: Eribulin mesylate 1.4 mg/m\^2 was administered as an intravenous (IV) infusion (over 2 to 5 minutes) on Days 1 and 8 of each 3-week cycle. Trastuzumab 8 mg/kg was administered as in IV infusion over a 90-minute period on Day 1 of Cycle 1. Thereafter, trastuzumab 6 mg/kg was administered as an IV infusion over a 30-minute period on Day 1 of each subsequent 21-day cycle.
Time to First Response	1.3 Months Interval 1.22 to 1.38

SECONDARY outcome

Timeframe: Date of a confirmed CR or PR was first documented to the date of PD or death (due to any cause and in the absence of PD), whichever occurred first, or date of data cutoff (12 Sep 2013), or up to approximately 2 years 9 months

Population: FAS included all participants who received at least one dose of study drug. Analyzed for responders only (n = 37).

Duration of response was defined for participants whose best overall response was CR or PR. Participants who died without reported PD were considered to have progressed on the day of their death. Participants who were alive at the end of the study without reported PD were censored on the date of their last tumor assessment.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate in Combination With Trastuzumab n=37 Participants Eribulin Mesylate: Eribulin mesylate 1.4 mg/m\^2 was administered as an intravenous (IV) infusion (over 2 to 5 minutes) on Days 1 and 8 of each 3-week cycle. Trastuzumab 8 mg/kg was administered as in IV infusion over a 90-minute period on Day 1 of Cycle 1. Thereafter, trastuzumab 6 mg/kg was administered as an IV infusion over a 30-minute period on Day 1 of each subsequent 21-day cycle.
Duration of Response (DOR)	11.1 Months Interval 6.7 to 17.77

SECONDARY outcome

Timeframe: Date of first dose of study drug to date of PD or death (from any cause) whichever came first, or date of data cutoff (12 Sep 2013), up to approximately 2 years 9 months

Population: FAS included all participants who received at least one dose of study drug.

PFS was defined as the time from the date of the first dose of study drug until the date of first documentation of PD or date of death from any cause, whichever occurred first. Participants who died without reported PD were considered to have progressed on the day of their death. Participants who were lost to follow-up or alive and without reported PD at the end of study were censored on the date of their last tumor assessment.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate in Combination With Trastuzumab n=52 Participants Eribulin Mesylate: Eribulin mesylate 1.4 mg/m\^2 was administered as an intravenous (IV) infusion (over 2 to 5 minutes) on Days 1 and 8 of each 3-week cycle. Trastuzumab 8 mg/kg was administered as in IV infusion over a 90-minute period on Day 1 of Cycle 1. Thereafter, trastuzumab 6 mg/kg was administered as an IV infusion over a 30-minute period on Day 1 of each subsequent 21-day cycle.
Progression-Free Survival (PFS)	11.6 Months Interval 9.13 to 13.93

SECONDARY outcome

Timeframe: Start of study treatment to date of PD or death, whichever occurred first, or date of data cutoff (12 Sep 2013), up to approximately 2 years 9 months

Population: FAS included all participants who received at least one dose of study drug.

Defined as the period from treatment start date to the date of PD or death, whichever occurred first. Participants who were alive without having PD as of the data cutoff date were censored as of their last tumor assessment. Calculated for participants who best response was SD.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate in Combination With Trastuzumab n=13 Participants Eribulin Mesylate: Eribulin mesylate 1.4 mg/m\^2 was administered as an intravenous (IV) infusion (over 2 to 5 minutes) on Days 1 and 8 of each 3-week cycle. Trastuzumab 8 mg/kg was administered as in IV infusion over a 90-minute period on Day 1 of Cycle 1. Thereafter, trastuzumab 6 mg/kg was administered as an IV infusion over a 30-minute period on Day 1 of each subsequent 21-day cycle.
Duration of Stable Disease (SD)	7.1 Months Interval 5.55 to 13.5

Adverse Events

Eribulin Mesylate in Combination With Trastuzumab

Serious events: 15 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Eribulin Mesylate in Combination With Trastuzumab n=52 participants at risk Eribulin Mesylate: Eribulin mesylate 1.4 mg/m\^2 was administered as an IV infusion (over 2 to 5 minutes) on Days 1 and 8 of each 3-week cycle. Trastuzumab 8 mg/kg was administered as in IV infusion over a 90-minute period on Day 1 of Cycle 1. Thereafter, trastuzumab 6 mg/kg was administered as an IV infusion over a 30-minute period on Day 1 of each subsequent 21-day cycle.
Blood and lymphatic system disorders Anaemia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Blood and lymphatic system disorders Febrile neutropenia	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Blood and lymphatic system disorders Neutropenia	15.4% 8/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Cardiac disorders Cardiac failure chronic	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Vomiting	5.8% 3/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Diarrhoea	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Gastric ulcer	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Gastritis	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Nausea	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
General disorders Fatigue	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
General disorders Pyrexia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Gastroenteritis	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Lobar pneumonia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Urinary tract infection	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Investigations Electrocardiogram T wave abnormal	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Investigations White blood cell count decreased	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Failure to thrive	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Hypercalcaemia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Hyperglycaemia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholangiocarcinoma	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Headache	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Neuropathy peripheral	5.8% 3/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Peripheral sensory neuropathy	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Surgical and medical procedures Modified radical mastectomy	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Vascular disorders Orthostatic hypotension	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.

Other adverse events

Other adverse events
Measure	Eribulin Mesylate in Combination With Trastuzumab n=52 participants at risk Eribulin Mesylate: Eribulin mesylate 1.4 mg/m\^2 was administered as an IV infusion (over 2 to 5 minutes) on Days 1 and 8 of each 3-week cycle. Trastuzumab 8 mg/kg was administered as in IV infusion over a 90-minute period on Day 1 of Cycle 1. Thereafter, trastuzumab 6 mg/kg was administered as an IV infusion over a 30-minute period on Day 1 of each subsequent 21-day cycle.
Blood and lymphatic system disorders Anaemia	25.0% 13/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Blood and lymphatic system disorders Febrile neutropenia	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Blood and lymphatic system disorders Leukocytosis	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Blood and lymphatic system disorders Leukopenia	17.3% 9/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Blood and lymphatic system disorders Lymphadenopathy	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Blood and lymphatic system disorders Neutropenia	59.6% 31/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Dyspepsia	19.2% 10/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Dysphagia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Eructation	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Blood and lymphatic system disorders Normochromic normocytic anaemia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Cardiac disorders Bundle branch block right	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Cardiac disorders Cardiac failure chronic	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Cardiac disorders Electrocardiogram QT prolonged	5.8% 3/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Cardiac disorders Palpitations	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Cardiac disorders Pericardial effusion	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Cardiac disorders Sinus tachycardia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Cardiac disorders Tachycardia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Ear and labyrinth disorders Ear discomfort	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Ear and labyrinth disorders Ear Pain	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Ear and labyrinth disorders External ear inflammation	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Ear and labyrinth disorders Vertigo	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Eye disorders Cataract	5.8% 3/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Eye disorders Dacryostenosis acquired	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Eye disorders Dry eye	5.8% 3/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Eye disorders Eye allergy	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Eye disorders Eye irritation	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Eye disorders Lacrimation increased	15.4% 8/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Eye disorders Vision blurred	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Eye disorders Visual impairment	9.6% 5/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Eye disorders Vitreous detachment	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Abdominal pain	11.5% 6/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Abdominal pain upper	9.6% 5/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Aphthous stomatitis	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Constipation	25.0% 13/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Diarrhoea	32.7% 17/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Dry mouth	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Faeces discoloured	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Gastric ulcer	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Gastritis	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Gastrooesophageal reflux disease	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Haematochezia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Haemorrhoids	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Lip pain	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Nausea	46.2% 24/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Oesophagitis	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Oral pain	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Proctalgia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Stomatitis	17.3% 9/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Swollen tongue	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Gastrointestinal disorders Vomiting	23.1% 12/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
General disorders Asthenia	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
General disorders Catheter site pain	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
General disorders Chest discomfort	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
General disorders Chest pain	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
General disorders Chills	15.4% 8/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
General disorders Face oedema	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
General disorders Fatigue	69.2% 36/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
General disorders Gait disturbance	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
General disorders Influenza like illness	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
General disorders Mucosal inflammation	5.8% 3/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
General disorders Oedema	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
General disorders Oedema peripheral	23.1% 12/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
General disorders Pain	5.8% 3/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
General disorders Pyrexia	23.1% 12/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
General disorders Thrombosis in device	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Hepatobiliary disorders Hepatic steatosis	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Immune system disorders Drug hypersensitivity	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Immune system disorders Food allergy	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Immune system disorders Multiple allergies	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Immune system disorders Seasonal allergy	5.8% 3/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Breast infection	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Cellulitis	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Ear infection	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Fungal skin infection	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Gastroenteritis	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Influenza	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Lobar pneumonia	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Nasopharyngitis	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Oral candidiasis	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Pharyngitis	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Pharyngotonsillitis	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Rhinitis	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Sinusitis	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Tooth infection	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Upper respiratory tract infection	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Urinary tract infection	13.5% 7/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Infections and infestations Vulvovaginal mycotic infection	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Injury, poisoning and procedural complications Ankle fracture	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Injury, poisoning and procedural complications Corneal abrasion	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Injury, poisoning and procedural complications Excoriation	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Injury, poisoning and procedural complications Fall	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Injury, poisoning and procedural complications Infusion related reaction	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Injury, poisoning and procedural complications Ligament sprain	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Injury, poisoning and procedural complications Meniscus injury	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Injury, poisoning and procedural complications Muscle strain	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Injury, poisoning and procedural complications Spinal compression fracture	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Investigations Alanine aminotransferase increased	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Investigations Aspartate aminotransferase increased	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Investigations Blood alkaline phosphatase increased	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Investigations Blood cholesterol increased	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Investigations Blood phosphorus decreased	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Investigations Ejection fraction decreased	5.8% 3/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Investigations Electrocardiogram T wave abnormal	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Investigations Electrocardiogram abnormal	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Investigations Vitamin D decreased	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Investigations Weight decreased	11.5% 6/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Investigations Weight increased	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Investigations White blood cell count decreased	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Decreased appetite	25.0% 13/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Dehydration	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Diabetes mellitus	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Failure to thrive	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Hypercalcaemia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Hyperglycaemia	5.8% 3/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Hyperphosphataemia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Hypertriglyceridaemia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Hyperuricaemia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Hypoalbuminaemia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Hypocalcaemia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Hypokalaemia	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Hypomagnesaemia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Hyponatraemia	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Hypophosphataemia	5.8% 3/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Metabolism and nutrition disorders Lactose intolerance	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Musculoskeletal and connective tissue disorders Arthralgia	9.6% 5/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Musculoskeletal and connective tissue disorders Back pain	15.4% 8/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Musculoskeletal and connective tissue disorders Bone pain	13.5% 7/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Musculoskeletal and connective tissue disorders Flank pain	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Musculoskeletal and connective tissue disorders Muscle spasms	13.5% 7/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Musculoskeletal and connective tissue disorders Muscular weakness	5.8% 3/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	9.6% 5/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Musculoskeletal and connective tissue disorders Myalgia	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Musculoskeletal and connective tissue disorders Myopathy	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Musculoskeletal and connective tissue disorders Neck pain	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Musculoskeletal and connective tissue disorders Pain in extremity	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholangiocarcinoma	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroma	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Ataxia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Balance disorder	5.8% 3/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Carpal tunnel syndrome	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Dizziness	15.4% 8/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Dysgeusia	23.1% 12/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Headache	19.2% 10/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Hypoaesthesia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Memory impairment	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Migraine	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Neuralgia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Neuropathy peripheral	59.6% 31/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Paraesthesia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Peripheral motor neuropathy	5.8% 3/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Peripheral sensorimotor neuropathy	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Peripheral sensory neuropathy	17.3% 9/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Peroneal nerve palsy	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Nervous system disorders Syncope	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Psychiatric disorders Anxiety	5.8% 3/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Psychiatric disorders Confusional state	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Psychiatric disorders Depression	11.5% 6/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Psychiatric disorders Insomnia	13.5% 7/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Renal and urinary disorders Bladder pain	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Renal and urinary disorders Chromaturia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Renal and urinary disorders Dysuria	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Renal and urinary disorders Haematuria	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Renal and urinary disorders Pollakiuria	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Renal and urinary disorders Urinary retention	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Reproductive system and breast disorders Bartholin's cyst	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Reproductive system and breast disorders Breast pain	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Reproductive system and breast disorders Vaginal haemorrhage	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Reproductive system and breast disorders Vulvovaginal discomfort	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Reproductive system and breast disorders Vulvovaginal dryness	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Atelectasis	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Cough	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Dysphonia	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Dyspnoea	13.5% 7/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Epistaxis	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.8% 3/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Oropharyngeal discomfort	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Painful respiration	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Paranasal sinus hypersecretion	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Productive cough	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Sinus congestion	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Skin and subcutaneous tissue disorders Alopecia	88.5% 46/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Skin and subcutaneous tissue disorders Dermatitis allergic	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Skin and subcutaneous tissue disorders Dermatitis contact	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Skin and subcutaneous tissue disorders Dry skin	5.8% 3/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Skin and subcutaneous tissue disorders Heat rash	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Skin and subcutaneous tissue disorders Night sweats	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Skin and subcutaneous tissue disorders Onychoclasis	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Skin and subcutaneous tissue disorders Pruritus	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Skin and subcutaneous tissue disorders Rash	9.6% 5/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Skin and subcutaneous tissue disorders Rash maculo-papular	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Skin and subcutaneous tissue disorders Rash pruritic	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Skin and subcutaneous tissue disorders Skin exfoliation	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Skin and subcutaneous tissue disorders Skin fissures	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	3.8% 2/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Skin and subcutaneous tissue disorders Telangiectasia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Surgical and medical procedures Modified radical mastectomy	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Vascular disorders Deep vein thrombosis	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Vascular disorders Flushing	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Vascular disorders Hot flush	7.7% 4/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Vascular disorders Hypertension	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Vascular disorders Hypotension	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Vascular disorders Jugular vein thrombosis	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Vascular disorders Lymphoedema	5.8% 3/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Vascular disorders Orthostatic hypotension	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Blood and lymphatic system disorders Thrombocytopenia	1.9% 1/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	13.5% 7/52 • From the date of signed informed consent until 30 days after discontinuation of study drug or until resolution, whichever occurred first. Up to approximately 2 years 10 months. Treatment-emergent adverse events and serious adverse events were reported. Safety Set included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. Study treatment toxicities were graded on a 5-point scale in accordance with Common Terminology Criteria for Adverse Events, version 4.0.

Additional Information

Eisai Medical Services

Eisai Inc.

Phone: 1-888-422-4743

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place