Trial Outcomes & Findings for A Treatment Combination for Patients With Unresectable Stage III or Stage IV Melanoma (NCT NCT00111007)

Last Updated: 2014-10-31

Results Overview

PFS was calculated as the time (days) from date of randomization to date of first observed DP (per modified Response Evaluation Criteria In Solid Tumors \[RECIST\] or clinical judgment, whichever was earlier: CR, PR, stable disease, progressive disease) or death due to any cause, if death occurred before progression was documented. The actual date of tumor assessments was used for this calculation. PFS for subjects without progression or death was censored at the last date of tumor evaluation. PFS for subjects who had no tumor assessments after baseline and did not die was censored at 1 day.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

270 participants

Primary outcome timeframe

Time from randomization to documented tumor progression or death (median time of 124 days)

Results posted on

2014-10-31

Participant Flow

The study was conducted from May 4 2005 to Jan 08 2009 (first subject's first visit to last subject's last visit) at 54 centers in 7 countries: Australia (6), Canada (6), France (6), Germany (10), Netherlands (2), United Kingdom (8), and United States (16).

Of 315 screened subjects, 270 were randomized (45 failed screening) and were valid for Intent-To-Treat (ITT) analyses (135 in each treatment group). One subject in each group did not receive treatment: 1 died and 1 withdrew consent. Thus, 268 subjects received treatment (134 in each group) and were valid for the safety analyses.

Participant milestones

Participant milestones
Measure	Sorafenib (Nexavar, BAY43-9006) Sorafenib, 400 mg orally, 2 tablets (200 mg each) bid (bis in die \[twice daily\]) on Study Days 2 to 19 + Paclitaxel (225 mg/m\^2 iv \[Intravenous\]) and Carboplatin (AUC \[area under the curve\] 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.	Carboplatin/Paclitaxel (C/P) Placebo, 2 tablets bid on Study Days 2-19 + Paclitaxel (225 mg/m\^2 iv) and Carboplatin (AUC 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.
Double-blind (DB) Treatment STARTED	135	135
Double-blind (DB) Treatment Received Treatment	134	134
Double-blind (DB) Treatment COMPLETED	27	24
Double-blind (DB) Treatment NOT COMPLETED	108	111
Active Follow-up STARTED	6	4
Active Follow-up COMPLETED	0	2
Active Follow-up NOT COMPLETED	6	2
Long Term Follow-up STARTED	101	107
Long Term Follow-up COMPLETED	54	62
Long Term Follow-up NOT COMPLETED	47	45

Reasons for withdrawal

Reasons for withdrawal
Measure	Sorafenib (Nexavar, BAY43-9006) Sorafenib, 400 mg orally, 2 tablets (200 mg each) bid (bis in die \[twice daily\]) on Study Days 2 to 19 + Paclitaxel (225 mg/m\^2 iv \[Intravenous\]) and Carboplatin (AUC \[area under the curve\] 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.	Carboplatin/Paclitaxel (C/P) Placebo, 2 tablets bid on Study Days 2-19 + Paclitaxel (225 mg/m\^2 iv) and Carboplatin (AUC 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.
Double-blind (DB) Treatment Adverse Event	12	4
Double-blind (DB) Treatment Death	5	2
Double-blind (DB) Treatment Protocol Violation	0	1
Double-blind (DB) Treatment Withdrawal by Subject	6	8
Double-blind (DB) Treatment Disease progression/recurrence/relapse	1	0
Double-blind (DB) Treatment Relapse	1	0
Double-blind (DB) Treatment Progression by clinical judgement	0	2
Double-blind (DB) Treatment Radiological and symptomatic progression	83	93
Double-blind (DB) Treatment Primary reason with other category	0	1
Active Follow-up Adverse Event	1	0
Active Follow-up Death	2	0
Active Follow-up Disease progression/recurrence/relapse	3	2
Long Term Follow-up Death	34	39
Long Term Follow-up Lost to Follow-up	1	1
Long Term Follow-up Withdrawal by Subject	0	1
Long Term Follow-up Disease progression/recurrence/relapse	2	1
Long Term Follow-up Missing	10	3

Baseline Characteristics

A Treatment Combination for Patients With Unresectable Stage III or Stage IV Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sorafenib (Nexavar, BAY43-9006) n=135 Participants Sorafenib, 400 mg orally, 2 tablets (200 mg each) bid (bis in die \[twice daily\]) on Study Days 2 to 19 + Paclitaxel (225 mg/m\^2 iv \[Intravenous\]) and Carboplatin (AUC \[area under the curve\] 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.	Carboplatin/Paclitaxel (C/P) n=135 Participants Placebo, 2 tablets bid on Study Days 2-19 + Paclitaxel (225 mg/m\^2 iv) and Carboplatin (AUC 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.	Total n=270 Participants Total of all reporting groups
Age, Continuous	56.0 years STANDARD_DEVIATION 12.8 • n=5 Participants	55.1 years STANDARD_DEVIATION 13.0 • n=7 Participants	55.5 years STANDARD_DEVIATION 57.0 • n=5 Participants
Age, Customized <65 years	97 participants n=5 Participants	92 participants n=7 Participants	189 participants n=5 Participants
Age, Customized 65 to 74 years	29 participants n=5 Participants	39 participants n=7 Participants	68 participants n=5 Participants
Age, Customized >=75 years	9 participants n=5 Participants	4 participants n=7 Participants	13 participants n=5 Participants
Sex: Female, Male Female	51 Participants n=5 Participants	48 Participants n=7 Participants	99 Participants n=5 Participants
Sex: Female, Male Male	84 Participants n=5 Participants	87 Participants n=7 Participants	171 Participants n=5 Participants
American Joint Committee on Cancer (AJCC) Stage at Study Entry Stage III or IV M1a	16 participants n=5 Participants	11 participants n=7 Participants	27 participants n=5 Participants
American Joint Committee on Cancer (AJCC) Stage at Study Entry Stage IV M1b	27 participants n=5 Participants	31 participants n=7 Participants	58 participants n=5 Participants
American Joint Committee on Cancer (AJCC) Stage at Study Entry Stage IV M1c	92 participants n=5 Participants	93 participants n=7 Participants	185 participants n=5 Participants
Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status 0	76 participants n=5 Participants	70 participants n=7 Participants	146 participants n=5 Participants
Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status 1	59 participants n=5 Participants	65 participants n=7 Participants	124 participants n=5 Participants

PRIMARY outcome

Timeframe: Time from randomization to documented tumor progression or death (median time of 124 days)

Population: PFS was analyzed for the intent to treat (ITT) population, defined as all subjects randomized to treatment. For the ITT population, subjects were included in the treatment group assigned at randomization, regardless of the treatment received.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=135 Participants Sorafenib, 400 mg orally, 2 tablets (200 mg each) bid (bis in die \[twice daily\]) on Study Days 2 to 19 + Paclitaxel (225 mg/m\^2 iv \[Intravenous\]) and Carboplatin (AUC \[area under the curve\] 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.	Carboplatin/Paclitaxel (C/P) n=135 Participants Placebo, 2 tablets bid on Study Days 2-19 + Paclitaxel (225 mg/m\^2 iv) and Carboplatin (AUC 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.
Progression Free Survival (PFS)	122 days Interval 83.0 to 162.0	125 days Interval 79.0 to 160.0

SECONDARY outcome

Timeframe: Time from randomization to death (median time of 294 days)

Population: OS was analyzed for the intent to treat (ITT) population, defined as all subjects randomized to treatment. For the ITT population, subjects were included in the treatment group assigned at randomization, regardless of the treatment received.

Overall survival (OS) was calculated as the number of days from date of randomization to death date. Subjects who had not died at the time of analysis were censored at their last contact date.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=135 Participants Sorafenib, 400 mg orally, 2 tablets (200 mg each) bid (bis in die \[twice daily\]) on Study Days 2 to 19 + Paclitaxel (225 mg/m\^2 iv \[Intravenous\]) and Carboplatin (AUC \[area under the curve\] 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.	Carboplatin/Paclitaxel (C/P) n=135 Participants Placebo, 2 tablets bid on Study Days 2-19 + Paclitaxel (225 mg/m\^2 iv) and Carboplatin (AUC 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.
Overall Survival (OS)	294 days Interval 247.0 to 321.0	294 days Interval 259.0 to 382.0

SECONDARY outcome

Timeframe: Time from randomization to documented tumor progression (median time of 126 days)

Population: TTP was analyzed for the intent to treat (ITT) population, defined as all subjects randomized to treatment. For the ITT population, subjects were included in the treatment group assigned at randomization, regardless of the treatment received.

TTP was calculated as the time (days) from date of randomization to date of first observed disease progression (DP) (per modified RECIST or clinical judgment, whichever was earlier: CR, PR, stable disease, progressive disease). The actual dates of tumor assessments were used for this calculation. TTP for subjects without disease progression at the time of analysis, including subjects with death prior to progression, was censored at the last date of tumor evaluation. TTP for subjects who had no tumor assessments after baseline was censored at 1 day.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=135 Participants Sorafenib, 400 mg orally, 2 tablets (200 mg each) bid (bis in die \[twice daily\]) on Study Days 2 to 19 + Paclitaxel (225 mg/m\^2 iv \[Intravenous\]) and Carboplatin (AUC \[area under the curve\] 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.	Carboplatin/Paclitaxel (C/P) n=135 Participants Placebo, 2 tablets bid on Study Days 2-19 + Paclitaxel (225 mg/m\^2 iv) and Carboplatin (AUC 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.
Time to Progression (TTP)	126 days Interval 90.0 to 167.0	126 days Interval 83.0 to 160.0

SECONDARY outcome

Timeframe: Time from initial response to documented tumor progression or death (median time of 197 days)

Population: DOR was analyzed for the intent to treat (ITT) population, defined as all subjects randomized to treatment. For the ITT population, subjects were included in the treatment group assigned at randomization, regardless of the treatment received.

Duration of response was defined as the time from the first documented objective response of Partial Response (PR: At least a 30% decrease in the sum of the longest diameter \[SLD\] of target lesions, taking as reference the baseline SLD or better) or Complete Response (CR: Disappearance of all target lesions), whichever was noted earlier, to disease progression or death (if death occurred before progression was documented). Duration of response for subjects who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=135 Participants Sorafenib, 400 mg orally, 2 tablets (200 mg each) bid (bis in die \[twice daily\]) on Study Days 2 to 19 + Paclitaxel (225 mg/m\^2 iv \[Intravenous\]) and Carboplatin (AUC \[area under the curve\] 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.	Carboplatin/Paclitaxel (C/P) n=135 Participants Placebo, 2 tablets bid on Study Days 2-19 + Paclitaxel (225 mg/m\^2 iv) and Carboplatin (AUC 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.
Duration of Response (DOR)	228 days Interval 42.0 to 420.0	166 days Interval 46.0 to 209.0

SECONDARY outcome

Timeframe: baseline and at visit when best response was noted (maximum treatment duration of 68.3 weeks)

Population: Change in ECOG PS was analyzed for the intent to treat (ITT) population, defined as all subjects randomized to treatment. For the ITT population, subjects were included in the treatment group assigned at randomization, regardless of the treatment received.

Change in ECOG PS is defined as an improvement (increase) or worsening (decrease) of at least one grade from the baseline ECOG score (from 0 \[fully active\] to 5 \[dead\]). Change in ECOG PS was recorded at the visit at which best confirmed response (BCR) using the modified RECIST (PR, CR, stable disease or Progressive Disease (PD)) was first noted (the change was 7% for both Sorafenib and Placebo). The BCR is the BCR recorded from the start of the treatment until DP/recurrence (taking as reference for DP, the smallest measurements recorded since treatment started).

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=135 Participants Sorafenib, 400 mg orally, 2 tablets (200 mg each) bid (bis in die \[twice daily\]) on Study Days 2 to 19 + Paclitaxel (225 mg/m\^2 iv \[Intravenous\]) and Carboplatin (AUC \[area under the curve\] 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.	Carboplatin/Paclitaxel (C/P) n=135 Participants Placebo, 2 tablets bid on Study Days 2-19 + Paclitaxel (225 mg/m\^2 iv) and Carboplatin (AUC 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status to the Visit When the Best Tumor Response Was Noted missing	10 participants	4 participants
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status to the Visit When the Best Tumor Response Was Noted better	9 participants	10 participants
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status to the Visit When the Best Tumor Response Was Noted no change	70 participants	82 participants
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status to the Visit When the Best Tumor Response Was Noted worse	46 participants	39 participants

Adverse Events

Sorafenib (Nexavar, BAY43-9006)

Serious events: 66 serious events

Other events: 132 other events

Deaths: 0 deaths

Carboplatin/Paclitaxel (C/P)

Serious events: 65 serious events

Other events: 134 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Therapeutic Area Head

BAYER

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Sorafenib (Nexavar, BAY43-9006) n=134 participants at risk Sorafenib, 400 mg orally, 2 tablets (200 mg each) bid (bis in die \[twice daily\]) on Study Days 2 to 19 + Paclitaxel (225 mg/m\^2 iv \[Intravenous\]) and Carboplatin (AUC \[area under the curve\] 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.	Carboplatin/Paclitaxel (C/P) n=134 participants at risk Placebo, 2 tablets bid on Study Days 2-19 + Paclitaxel (225 mg/m\^2 iv) and Carboplatin (AUC 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.
Immune system disorders allergic reaction	3.0% 4/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	1.5% 2/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Blood and lymphatic system disorders neutrophils	11.2% 15/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	5.2% 7/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Blood and lymphatic system disorders hemoglobin	2.2% 3/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	6.0% 8/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Blood and lymphatic system disorders platelets	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	2.2% 3/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Blood and lymphatic system disorders leukocytes	1.5% 2/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Cardiac disorders supraventricular arrhythmia, atrial flutter	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Cardiac disorders supraventricular arrhythmia, supraventricular extrasystoles (pac; premature nodal/junction contr)	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Cardiac disorders supraventricular arrhythmia, supraventricular arrhythmia NOS	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Cardiac disorders tachycardia	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Cardiac disorders vasovagal episode	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Cardiac disorders hypotension	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	1.5% 2/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Cardiac disorders cardiac ischemia / infarction	1.5% 2/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Cardiac disorders cardiac general - other	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Cardiac disorders left ventricular diastolic dysfunction	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Cardiac disorders pericarditis	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
General disorders death not associated with CTCAE term, disease progression NOS	1.5% 2/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
General disorders death not associated with CTCAE term, death NOS	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Endocrine disorders diabetes	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
General disorders fever	2.2% 3/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	3.7% 5/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
General disorders fatigue	1.5% 2/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	3.0% 4/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
General disorders constitutional symptoms - other	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	3.0% 4/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders vomiting	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	3.0% 4/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders diarrhea	1.5% 2/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	1.5% 2/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders dehydration	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	1.5% 2/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders obstruction, GI, small bowel NOS	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	1.5% 2/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders anorexia	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	1.5% 2/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders constipation	1.5% 2/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders nausea	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders colitis	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders esophagitis	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders fistula, GI, esophagus	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Vascular disorders CNS hemorrhage	1.5% 2/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	1.5% 2/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Vascular disorders hemorrhage - other	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Vascular disorders hemorrhage, GI, lower GI NOS	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Vascular disorders hemorrhage with surgery	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Vascular disorders hemorrhage pulmonary, respiratory tract NOS	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Vascular disorders hemorrhage, GU, bladder	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Vascular disorders hemorrhage, GU, urinary NOS	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Hepatobiliary disorders liver dysfunction	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Hepatobiliary disorders cholecystitis	0.75% 1/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)

Other adverse events
Measure	Sorafenib (Nexavar, BAY43-9006) n=134 participants at risk Sorafenib, 400 mg orally, 2 tablets (200 mg each) bid (bis in die \[twice daily\]) on Study Days 2 to 19 + Paclitaxel (225 mg/m\^2 iv \[Intravenous\]) and Carboplatin (AUC \[area under the curve\] 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.	Carboplatin/Paclitaxel (C/P) n=134 participants at risk Placebo, 2 tablets bid on Study Days 2-19 + Paclitaxel (225 mg/m\^2 iv) and Carboplatin (AUC 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.
Immune system disorders allergic reaction	6.0% 8/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	7.5% 10/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Blood and lymphatic system disorders neutrophils	50.7% 68/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	53.0% 71/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Blood and lymphatic system disorders platelets	46.3% 62/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	29.9% 40/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Blood and lymphatic system disorders hemoglobin	24.6% 33/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	32.8% 44/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Blood and lymphatic system disorders leukocytes	26.9% 36/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	28.4% 38/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Blood and lymphatic system disorders lymphopenia	6.0% 8/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	3.7% 5/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Cardiac disorders hypertension	8.2% 11/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	4.5% 6/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
General disorders fatigue	76.1% 102/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	59.0% 79/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
General disorders insomnia	19.4% 26/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	18.7% 25/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
General disorders fever	11.9% 16/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	8.2% 11/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
General disorders sweating	7.5% 10/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	11.9% 16/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
General disorders weight loss	11.9% 16/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	6.7% 9/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
General disorders rigors / chills	7.5% 10/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	6.0% 8/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
General disorders constitutional symptoms - other	2.2% 3/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	5.2% 7/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders nausea	53.0% 71/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	53.7% 72/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders diarrhea	47.8% 64/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	26.9% 36/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders constipation	29.9% 40/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	31.3% 42/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders vomiting	24.6% 33/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	23.9% 32/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders anorexia	23.9% 32/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	11.2% 15/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders mucositis (functional / symptomatic), oral cavity	12.7% 17/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	8.2% 11/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders taste alteration	8.2% 11/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	9.7% 13/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders heartburn	9.0% 12/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	8.2% 11/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders GI - other	9.7% 13/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	4.5% 6/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders dry mouth	5.2% 7/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	2.2% 3/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Gastrointestinal disorders flatulence	5.2% 7/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	2.2% 3/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Vascular disorders hemorrhage pulmonary, nose	13.4% 18/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	7.5% 10/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Infections and infestations infection - other	5.2% 7/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	6.0% 8/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Infections and infestations infection with normal ANC, upper airway NOS	5.2% 7/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	4.5% 6/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Infections and infestations infection with unknown ANC, skin (cellulitis)	5.2% 7/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	0.00% 0/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Blood and lymphatic system disorders edema: limb	10.4% 14/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	13.4% 18/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Musculoskeletal and connective tissue disorders musculoskeletal - other	6.0% 8/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	4.5% 6/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Metabolism and nutrition disorders hypokalemia	6.7% 9/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	8.2% 11/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Metabolism and nutrition disorders hypomagnesemia	3.7% 5/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	7.5% 10/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Metabolism and nutrition disorders hypophosphatemia	6.0% 8/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	3.0% 4/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Metabolism and nutrition disorders lipase	5.2% 7/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	2.2% 3/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Nervous system disorders neuropathy: sensory	66.4% 89/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	64.9% 87/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Nervous system disorders dizziness	15.7% 21/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	14.2% 19/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Nervous system disorders mood alteration, depression	6.7% 9/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	8.2% 11/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Nervous system disorders neuropathy: motor	5.2% 7/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	3.7% 5/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)
Nervous system disorders neurology - other	6.0% 8/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)	3.0% 4/134 Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), Genito-Urinary (GU), National Cancer Institute (NCI), Not Otherwise Specified (NOS)