Trial Outcomes & Findings for A Study of Gemcitabine and Carboplatin (Plus Herceptin in Human Epidermal Growth Factor Receptor 2 Positive [HER2+] Patients) With Metastatic Breast Cancer (NCT NCT00191451)

NCT ID: NCT00191451

Last Updated: 2009-11-20

Results Overview

Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that do not meet above criteria.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 150 participants
• Primary outcome timeframe: baseline to disease progression/recurrence (up to 3.5 years)
• Results posted on: 2009-11-20

Participant Flow

Participant milestones

Measure	HER2+ Human Epidermal growth factor Receptor 2 positive: Gemcitabine + Carboplatin + Herceptin. Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion); Herceptin: Day 1 of 14 day cycle (Cycle 1): 8 milligrams per kilogram (mg/kg) intravenous (IV) (90 minute infusion). Day 1 of 14 day cycle (Cycles 2-9): 4 mg/kg IV (30 minute infusion). Day 1 of 21 day cycle (Cycles 10+): 6 mg/kg IV (30 minute infusion).	HER2- (Taxane-) Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-naive patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).	HER2- (Taxane+) Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-pretreated patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).
Overall Study STARTED	50	51	49
Overall Study Received at Least One Dose of Study Drug	50	48	47
Overall Study COMPLETED	43	37	35
Overall Study NOT COMPLETED	7	14	14

Reasons for withdrawal

Measure	HER2+ Human Epidermal growth factor Receptor 2 positive: Gemcitabine + Carboplatin + Herceptin. Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion); Herceptin: Day 1 of 14 day cycle (Cycle 1): 8 milligrams per kilogram (mg/kg) intravenous (IV) (90 minute infusion). Day 1 of 14 day cycle (Cycles 2-9): 4 mg/kg IV (30 minute infusion). Day 1 of 21 day cycle (Cycles 10+): 6 mg/kg IV (30 minute infusion).	HER2- (Taxane-) Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-naive patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).	HER2- (Taxane+) Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-pretreated patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).
Overall Study Withdrawal by Subject	2	3	5
Overall Study Physician Decision	2	9	6
Overall Study Sponsor Decision	1	0	0
Overall Study Ineligible	0	1	0
Overall Study Reason Not Specified	2	1	3

Baseline Characteristics

A Study of Gemcitabine and Carboplatin (Plus Herceptin in Human Epidermal Growth Factor Receptor 2 Positive [HER2+] Patients) With Metastatic Breast Cancer

Baseline characteristics by cohort

Measure	HER2+ n=50 Participants Human Epidermal growth factor Receptor 2 positive: Gemcitabine + Carboplatin + Herceptin. Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion); Herceptin: Day 1 of 14 day cycle (Cycle 1): 8 milligrams per kilogram (mg/kg) intravenous (IV) (90 minute infusion). Day 1 of 14 day cycle (Cycles 2-9): 4 mg/kg IV (30 minute infusion). Day 1 of 21 day cycle (Cycles 10+): 6 mg/kg IV (30 minute infusion).	HER2- (Taxane-) n=51 Participants Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-naive patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).	HER2- (Taxane+) n=49 Participants Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-pretreated patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).	Total n=150 Participants Total of all reporting groups
Age Continuous	56.1 years STANDARD_DEVIATION 9.45 • n=93 Participants	55.7 years STANDARD_DEVIATION 11.17 • n=4 Participants	54.8 years STANDARD_DEVIATION 9.92 • n=27 Participants	55.55 years STANDARD_DEVIATION 10.16 • n=483 Participants
Sex: Female, Male Female	50 Participants n=93 Participants	51 Participants n=4 Participants	49 Participants n=27 Participants	150 Participants n=483 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Region of Enrollment United States	50 participants n=93 Participants	51 participants n=4 Participants	49 participants n=27 Participants	150 participants n=483 Participants
Eastern Cooperative Oncology Group Performance Status 0 - Fully Active	41 participants n=93 Participants	36 participants n=4 Participants	32 participants n=27 Participants	109 participants n=483 Participants
Eastern Cooperative Oncology Group Performance Status 1 - Ambulatory, Restricted Strenuous Activity	8 participants n=93 Participants	14 participants n=4 Participants	17 participants n=27 Participants	39 participants n=483 Participants
Eastern Cooperative Oncology Group Performance Status 2 - Ambulatory, No Work Activities	1 participants n=93 Participants	1 participants n=4 Participants	0 participants n=27 Participants	2 participants n=483 Participants
Race/Ethnicity Caucasian	31 participants n=93 Participants	42 participants n=4 Participants	36 participants n=27 Participants	109 participants n=483 Participants
Race/Ethnicity Black	8 participants n=93 Participants	5 participants n=4 Participants	11 participants n=27 Participants	24 participants n=483 Participants
Race/Ethnicity Hispanic	7 participants n=93 Participants	4 participants n=4 Participants	1 participants n=27 Participants	12 participants n=483 Participants
Race/Ethnicity Other	4 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants	5 participants n=483 Participants

PRIMARY outcome

Timeframe: baseline to disease progression/recurrence (up to 3.5 years)

Population: Efficacy evaluable subjects include all subjects who received at least 2 cycles of treatment with at least 1 follow-up tumor assessment, and did not violate the protocol in any fundamental manner related to the evaluation of efficacy.

Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that do not meet above criteria.

Outcome measures

Measure	HER2+ n=50 Participants Human Epidermal growth factor Receptor 2 positive: Gemcitabine + Carboplatin + Herceptin. Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion); Herceptin: Day 1 of 14 day cycle (Cycle 1): 8 milligrams per kilogram (mg/kg) intravenous (IV) (90 minute infusion). Day 1 of 14 day cycle (Cycles 2-9): 4 mg/kg IV (30 minute infusion). Day 1 of 21 day cycle (Cycles 10+): 6 mg/kg IV (30 minute infusion).	HER2- (Taxane-) n=47 Participants Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-naive patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).	HER2- (Taxane+) n=47 Participants Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-pretreated patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).
Overall Tumor Response Complete Response (CR)	6 participants	0 participants	1 participants
Overall Tumor Response Partial Response (PR)	26 participants	13 participants	15 participants
Overall Tumor Response Stable Disease (SD)	12 participants	20 participants	13 participants
Overall Tumor Response Progressive Disease (PD)	4 participants	12 participants	17 participants
Overall Tumor Response Not Evaluable (NE)	2 participants	2 participants	1 participants

SECONDARY outcome

Timeframe: date of response (CR or PR) until the first date of documented progression or death from any cause (up to 3.5 years)

Population: Number of patients with complete or partial response. Censored patients: 6 in HER2+, 6 in HER2- (Taxane-), and 5 in HER2- (Taxane+).

Among tumor responders, the duration of tumor response is measured from the date of response (complete response [CR] or partial response [PR]) until the first date of documented progression or death from any cause. Duration of tumor response will be censored at the date of the last follow-up visit for tumor responders who are still alive and who have not progressed.

Outcome measures

Measure	HER2+ n=32 Participants Human Epidermal growth factor Receptor 2 positive: Gemcitabine + Carboplatin + Herceptin. Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion); Herceptin: Day 1 of 14 day cycle (Cycle 1): 8 milligrams per kilogram (mg/kg) intravenous (IV) (90 minute infusion). Day 1 of 14 day cycle (Cycles 2-9): 4 mg/kg IV (30 minute infusion). Day 1 of 21 day cycle (Cycles 10+): 6 mg/kg IV (30 minute infusion).	HER2- (Taxane-) n=13 Participants Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-naive patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).	HER2- (Taxane+) n=16 Participants Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-pretreated patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).
Duration of Response	6.9 months Interval 2.0 to 42.1	6.4 months Interval 3.5 to 29.7	5.6 months Interval 2.3 to 14.8

SECONDARY outcome

Timeframe: Baseline to 3.5 years

Population: Number of patients who received at least one dose of study drug.

Outcome measures

Measure	HER2+ n=50 Participants Human Epidermal growth factor Receptor 2 positive: Gemcitabine + Carboplatin + Herceptin. Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion); Herceptin: Day 1 of 14 day cycle (Cycle 1): 8 milligrams per kilogram (mg/kg) intravenous (IV) (90 minute infusion). Day 1 of 14 day cycle (Cycles 2-9): 4 mg/kg IV (30 minute infusion). Day 1 of 21 day cycle (Cycles 10+): 6 mg/kg IV (30 minute infusion).	HER2- (Taxane-) n=48 Participants Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-naive patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).	HER2- (Taxane+) n=47 Participants Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-pretreated patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).
Number of Patients Who Experienced Alopecia	21 participants	17 participants	16 participants

SECONDARY outcome

Timeframe: randomization date to the earliest date of the first documented disease progression date or the date of death if the patient dies due to study disease (up to 3.5 years)

Population: Intent to treat population: all randomized patients. Censored patients: 10 in HER2+, 20 in HER2- (Taxane-), and 12 in HER2- (Taxane+).

If a patient is lost to follow-up, the patient will be censored as of the last date of contact. Patients who start a new treatment before they progress will be censored as of the date of start of the new treatment. If a patient died due to reason other than study disease, and patient has not progressed or received any new treatment, TTP is censored at the date of death.

Outcome measures

Measure	HER2+ n=50 Participants Human Epidermal growth factor Receptor 2 positive: Gemcitabine + Carboplatin + Herceptin. Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion); Herceptin: Day 1 of 14 day cycle (Cycle 1): 8 milligrams per kilogram (mg/kg) intravenous (IV) (90 minute infusion). Day 1 of 14 day cycle (Cycles 2-9): 4 mg/kg IV (30 minute infusion). Day 1 of 21 day cycle (Cycles 10+): 6 mg/kg IV (30 minute infusion).	HER2- (Taxane-) n=51 Participants Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-naive patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).	HER2- (Taxane+) n=49 Participants Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-pretreated patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).
Time to Disease Progression (TTP)	7.2 months Interval 6.0 to 9.0	5.6 months Interval 3.3 to 7.2	4.6 months Interval 1.8 to 9.0

SECONDARY outcome

Timeframe: 1 Year, 2 Years

Population: Intent to treat population: all randomized patients. Censored patients: 31 HER2+; 19 HER2- (Taxane-); 9 HER2- (Taxane+).

Kaplan-Meier estimates of overall survival (percentage of patients surviving) at 1 year and 2 years.

Outcome measures

Measure	HER2+ n=50 Participants Human Epidermal growth factor Receptor 2 positive: Gemcitabine + Carboplatin + Herceptin. Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion); Herceptin: Day 1 of 14 day cycle (Cycle 1): 8 milligrams per kilogram (mg/kg) intravenous (IV) (90 minute infusion). Day 1 of 14 day cycle (Cycles 2-9): 4 mg/kg IV (30 minute infusion). Day 1 of 21 day cycle (Cycles 10+): 6 mg/kg IV (30 minute infusion).	HER2- (Taxane-) n=51 Participants Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-naive patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).	HER2- (Taxane+) n=49 Participants Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-pretreated patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).
Percentage of Patients With Overall Survival at 1 Year and 2 Years 1 Year Overall Survival	90.0 percentage of participants	67.5 percentage of participants	47.8 percentage of participants
Percentage of Patients With Overall Survival at 1 Year and 2 Years 2 Year Overall Survival	73.3 percentage of participants	41.4 percentage of participants	20.5 percentage of participants

Adverse Events

HER2+

Serious events: 10 serious events

Other events: 50 other events

Deaths: 0 deaths

HER2- (Taxane-)

Serious events: 11 serious events

Other events: 48 other events

Deaths: 0 deaths

HER2- (Taxane+)

Serious events: 10 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Measure	HER2+ n=50 participants at risk Human Epidermal growth factor Receptor 2 positive: Gemcitabine + Carboplatin + Herceptin. Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion); Herceptin: Day 1 of 14 day cycle (Cycle 1): 8 milligrams per kilogram (mg/kg) intravenous (IV) (90 minute infusion). Day 1 of 14 day cycle (Cycles 2-9): 4 mg/kg IV (30 minute infusion). Day 1 of 21 day cycle (Cycles 10+): 6 mg/kg IV (30 minute infusion).	HER2- (Taxane-) n=48 participants at risk Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-naive patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).	HER2- (Taxane+) n=47 participants at risk Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-pretreated patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).
Blood and lymphatic system disorders Anaemia	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.3% 4/48 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.3% 2/47 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Blood and lymphatic system disorders Neutropenia	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.2% 2/48 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.2% 2/48 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Cardiac disorders Diastolic dysfunction	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Cardiac disorders Tachycardia	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Gastrointestinal disorders Intestinal obstruction	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Gastrointestinal disorders Nausea	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Gastrointestinal disorders Oesophageal spasm	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Gastrointestinal disorders Oesophagitis	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Gastrointestinal disorders Retching	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Gastrointestinal disorders Vomiting	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Chest discomfort	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Chest pain	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Disease progression	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Localised oedema	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Mucous membrane disorder	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Multi-organ failure	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Oedema peripheral	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Pain	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Pyrexia	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.2% 2/48 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Hepatobiliary disorders Jaundice	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Immune system disorders Hypersensitivity	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Infections and infestations Catheter sepsis	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Infections and infestations Fungaemia	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Infections and infestations Pneumonia	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Infections and infestations Sepsis	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Infections and infestations Wound infection	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Metabolism and nutrition disorders Dehydration	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Metabolism and nutrition disorders Hypovolaemia	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Metabolism and nutrition disorders Malnutrition	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Musculoskeletal and connective tissue disorders Back pain	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Nervous system disorders Dizziness	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Nervous system disorders Headache	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Nervous system disorders Intracranial hypotension	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Nervous system disorders Neurological symptom	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Nervous system disorders Somnolence	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Nervous system disorders Spinal cord compression	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Nervous system disorders Syncope	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.0% 1/50 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.3% 4/48 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.3% 2/47 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Respiratory, thoracic and mediastinal disorders Haemothorax	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Respiratory, thoracic and mediastinal disorders Orthopnoea	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Vascular disorders Vena cava thrombosis	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).

Other adverse events

Measure	HER2+ n=50 participants at risk Human Epidermal growth factor Receptor 2 positive: Gemcitabine + Carboplatin + Herceptin. Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion); Herceptin: Day 1 of 14 day cycle (Cycle 1): 8 milligrams per kilogram (mg/kg) intravenous (IV) (90 minute infusion). Day 1 of 14 day cycle (Cycles 2-9): 4 mg/kg IV (30 minute infusion). Day 1 of 21 day cycle (Cycles 10+): 6 mg/kg IV (30 minute infusion).	HER2- (Taxane-) n=48 participants at risk Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-naive patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).	HER2- (Taxane+) n=47 participants at risk Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-pretreated patients). Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).
Blood and lymphatic system disorders Anaemia	62.0% 31/50 • Number of events 60 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	50.0% 24/48 • Number of events 35 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	46.8% 22/47 • Number of events 35 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Blood and lymphatic system disorders Leukopenia	32.0% 16/50 • Number of events 47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	41.7% 20/48 • Number of events 64 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	21.3% 10/47 • Number of events 29 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Blood and lymphatic system disorders Lymphopenia	8.0% 4/50 • Number of events 11 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.2% 2/48 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Blood and lymphatic system disorders Neutropenia	70.0% 35/50 • Number of events 102 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	77.1% 37/48 • Number of events 109 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	59.6% 28/47 • Number of events 77 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Blood and lymphatic system disorders Thrombocytopenia	26.0% 13/50 • Number of events 34 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	35.4% 17/48 • Number of events 47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	31.9% 15/47 • Number of events 32 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Cardiac disorders Tachycardia	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.2% 3/48 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.4% 3/47 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Ear and labyrinth disorders Vertigo	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	10.4% 5/48 • Number of events 7 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Eye disorders Lacrimation increased	6.0% 3/50 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.2% 2/48 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Eye disorders Vision blurred	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.2% 3/48 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Gastrointestinal disorders Abdominal pain upper	4.0% 2/50 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.2% 3/48 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.3% 2/47 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Gastrointestinal disorders Constipation	38.0% 19/50 • Number of events 27 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	39.6% 19/48 • Number of events 30 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	29.8% 14/47 • Number of events 18 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Gastrointestinal disorders Diarrhoea	20.0% 10/50 • Number of events 17 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	27.1% 13/48 • Number of events 20 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	17.0% 8/47 • Number of events 9 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Gastrointestinal disorders Haemorrhoids	8.0% 4/50 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.3% 2/47 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Gastrointestinal disorders Nausea	54.0% 27/50 • Number of events 59 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	68.8% 33/48 • Number of events 71 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	46.8% 22/47 • Number of events 44 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Gastrointestinal disorders Stomatitis	14.0% 7/50 • Number of events 8 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	12.5% 6/48 • Number of events 6 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.3% 2/47 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Gastrointestinal disorders Vomiting	26.0% 13/50 • Number of events 17 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	37.5% 18/48 • Number of events 32 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	25.5% 12/47 • Number of events 21 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Asthenia	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	12.5% 6/48 • Number of events 8 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.4% 3/47 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Chest discomfort	6.0% 3/50 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Chest pain	8.0% 4/50 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	10.4% 5/48 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	12.8% 6/47 • Number of events 6 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Chills	8.0% 4/50 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	14.6% 7/48 • Number of events 9 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	10.6% 5/47 • Number of events 6 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Fatigue	74.0% 37/50 • Number of events 70 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	72.9% 35/48 • Number of events 56 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	63.8% 30/47 • Number of events 50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Mucosal inflammation	2.0% 1/50 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.2% 3/48 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.5% 4/47 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Oedema	8.0% 4/50 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	10.4% 5/48 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.3% 2/47 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Oedema peripheral	10.0% 5/50 • Number of events 7 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	12.5% 6/48 • Number of events 8 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	21.3% 10/47 • Number of events 11 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Pain	6.0% 3/50 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.2% 2/48 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	12.8% 6/47 • Number of events 6 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
General disorders Pyrexia	12.0% 6/50 • Number of events 7 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.3% 4/48 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	10.6% 5/47 • Number of events 8 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Infections and infestations Rhinitis	12.0% 6/50 • Number of events 6 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.2% 2/48 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Infections and infestations Upper respiratory tract infection	10.0% 5/50 • Number of events 6 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.3% 4/48 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.4% 3/47 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Infections and infestations Urinary tract infection	4.0% 2/50 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.3% 4/48 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.3% 2/47 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Injury, poisoning and procedural complications Contusion	2.0% 1/50 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.4% 3/47 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Investigations Alanine aminotransferase	12.0% 6/50 • Number of events 8 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	14.6% 7/48 • Number of events 7 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Investigations Alanine aminotransferase increased	20.0% 10/50 • Number of events 16 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	20.8% 10/48 • Number of events 14 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	14.9% 7/47 • Number of events 8 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Investigations Aspartate aminotransferase	8.0% 4/50 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	10.4% 5/48 • Number of events 6 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Investigations Aspartate aminotransferase increased	20.0% 10/50 • Number of events 16 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	25.0% 12/48 • Number of events 16 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	10.6% 5/47 • Number of events 7 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Investigations Blood alkaline phosphatase	6.0% 3/50 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Investigations Blood alkaline phosphatase increased	16.0% 8/50 • Number of events 10 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	10.4% 5/48 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	10.6% 5/47 • Number of events 6 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Investigations Blood calcium decreased	4.0% 2/50 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.2% 3/48 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Investigations Blood glucose increased	4.0% 2/50 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.2% 3/48 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.3% 2/47 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Investigations Blood lactate dehydrogenase increased	6.0% 3/50 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Investigations Haemoglobin	22.0% 11/50 • Number of events 11 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	18.8% 9/48 • Number of events 10 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	14.9% 7/47 • Number of events 9 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Investigations Haemoglobin decreased	4.0% 2/50 • Number of events 6 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	14.6% 7/48 • Number of events 11 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.3% 2/47 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Investigations Neutrophil count	10.0% 5/50 • Number of events 10 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.2% 2/48 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Investigations Platelet count	8.0% 4/50 • Number of events 11 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	16.7% 8/48 • Number of events 16 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	14.9% 7/47 • Number of events 12 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Investigations Platelet count increased	6.0% 3/50 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Investigations White blood cell count	12.0% 6/50 • Number of events 15 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	10.4% 5/48 • Number of events 10 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	17.0% 8/47 • Number of events 15 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Investigations White blood cell count decreased	6.0% 3/50 • Number of events 9 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.2% 2/48 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.4% 3/47 • Number of events 6 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Metabolism and nutrition disorders Anorexia	16.0% 8/50 • Number of events 11 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	22.9% 11/48 • Number of events 13 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	21.3% 10/47 • Number of events 11 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Metabolism and nutrition disorders Dehydration	2.0% 1/50 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.2% 3/48 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.5% 4/47 • Number of events 10 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Metabolism and nutrition disorders Hyperglycaemia	30.0% 15/50 • Number of events 23 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	16.7% 8/48 • Number of events 13 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.5% 4/47 • Number of events 7 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Metabolism and nutrition disorders Hypoalbuminaemia	8.0% 4/50 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Metabolism and nutrition disorders Hypocalcaemia	6.0% 3/50 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Metabolism and nutrition disorders Hypokalaemia	10.0% 5/50 • Number of events 7 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.3% 4/48 • Number of events 6 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Metabolism and nutrition disorders Hyponatraemia	6.0% 3/50 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Musculoskeletal and connective tissue disorders Arthralgia	18.0% 9/50 • Number of events 12 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	18.8% 9/48 • Number of events 16 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	10.6% 5/47 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Musculoskeletal and connective tissue disorders Back pain	14.0% 7/50 • Number of events 7 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	10.4% 5/48 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.5% 4/47 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.2% 3/48 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Musculoskeletal and connective tissue disorders Muscle spasms	4.0% 2/50 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.2% 3/48 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.3% 2/47 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Musculoskeletal and connective tissue disorders Muscular weakness	4.0% 2/50 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.3% 4/48 • Number of events 6 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.3% 2/47 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	6.0% 3/50 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.2% 2/48 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	10.6% 5/47 • Number of events 7 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	8.0% 4/50 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.3% 4/48 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.5% 4/47 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Musculoskeletal and connective tissue disorders Myalgia	24.0% 12/50 • Number of events 19 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	12.5% 6/48 • Number of events 12 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/50 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.4% 3/47 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Musculoskeletal and connective tissue disorders Pain in extremity	8.0% 4/50 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	12.5% 6/48 • Number of events 9 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	10.6% 5/47 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Nervous system disorders Dizziness	8.0% 4/50 • Number of events 6 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	20.8% 10/48 • Number of events 15 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.5% 4/47 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Nervous system disorders Dysgeusia	10.0% 5/50 • Number of events 10 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	14.6% 7/48 • Number of events 9 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.4% 3/47 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Nervous system disorders Hypoaesthesia	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.5% 4/47 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Nervous system disorders Neuropathy peripheral	8.0% 4/50 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.2% 2/48 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.5% 4/47 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Nervous system disorders Paraesthesia	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.3% 4/48 • Number of events 6 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.3% 2/47 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Nervous system disorders Peripheral sensory neuropathy	4.0% 2/50 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.3% 4/48 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Psychiatric disorders Anxiety	14.0% 7/50 • Number of events 7 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.3% 4/48 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	17.0% 8/47 • Number of events 8 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Psychiatric disorders Depression	6.0% 3/50 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.2% 3/48 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	14.9% 7/47 • Number of events 7 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Psychiatric disorders Insomnia	18.0% 9/50 • Number of events 9 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	22.9% 11/48 • Number of events 12 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.5% 4/47 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Reproductive system and breast disorders Breast pain	6.0% 3/50 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.2% 2/48 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Respiratory, thoracic and mediastinal disorders Cough	32.0% 16/50 • Number of events 24 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	22.9% 11/48 • Number of events 14 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	21.3% 10/47 • Number of events 13 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Respiratory, thoracic and mediastinal disorders Dyspnoea	22.0% 11/50 • Number of events 14 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	14.6% 7/48 • Number of events 10 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	23.4% 11/47 • Number of events 12 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.2% 3/48 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/47 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Respiratory, thoracic and mediastinal disorders Nasal congestion	10.0% 5/50 • Number of events 6 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Respiratory, thoracic and mediastinal disorders Paranasal sinus hypersecretion	6.0% 3/50 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	2.0% 1/50 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.3% 4/48 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.3% 2/47 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Skin and subcutaneous tissue disorders Alopecia	42.0% 21/50 • Number of events 22 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	35.4% 17/48 • Number of events 22 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	34.0% 16/47 • Number of events 16 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Skin and subcutaneous tissue disorders Dry skin	4.0% 2/50 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	0.00% 0/48 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.4% 3/47 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Skin and subcutaneous tissue disorders Erythema	10.0% 5/50 • Number of events 6 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Skin and subcutaneous tissue disorders Hyperhidrosis	4.0% 2/50 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.2% 3/48 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Skin and subcutaneous tissue disorders Nail disorder	6.0% 3/50 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/48 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	2.1% 1/47 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Skin and subcutaneous tissue disorders Night sweats	4.0% 2/50 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	4.2% 2/48 • Number of events 2 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.4% 3/47 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Skin and subcutaneous tissue disorders Pruritus	12.0% 6/50 • Number of events 7 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.2% 3/48 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.5% 4/47 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Skin and subcutaneous tissue disorders Rash	22.0% 11/50 • Number of events 14 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	14.6% 7/48 • Number of events 9 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	10.6% 5/47 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Vascular disorders Hot flush	8.0% 4/50 • Number of events 5 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	14.6% 7/48 • Number of events 8 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	8.5% 4/47 • Number of events 4 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).
Vascular disorders Lymphoedema	2.0% 1/50 • Number of events 1 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.2% 3/48 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).	6.4% 3/47 • Number of events 3 Adverse events are provided for all patients who received at least one dose of study drug. Adverse events represent all grades (I-IV).

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

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

Restriction type: GT60