Trial Outcomes & Findings for Carboplatin and Paclitaxel With or Without Bevacizumab in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer (NCT NCT00262847)

Last Updated: 2019-07-23

Results Overview

Median progression-free survival (PFS). Onset of progression could be based on radiographic (RECIST) criteria or rising CA-125 (GCIG criteria).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1873 participants

Primary outcome timeframe

From study entry until first disease progression, death or date of last contact, up to 6 years

Results posted on

2019-07-23

Participant Flow

Between October 2005 and June 2009, 1873 women were enrolled from 336 institutions in the United States, Canada, South Korea, and Japan.

Participant milestones

Participant milestones
Measure	Arm I (Placebo, Paclitaxel, Carboplatin) Control therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus placebo (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab) Bevacizumab-initiation therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Arm III (Paclitaxel, Carboplatin, Bevacizumab) Bevacizumab-throughout therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received bevacizumab, 15 mg/kg every 3 weeks.
Overall Study STARTED	625	625	623
Overall Study COMPLETED	107	112	227
Overall Study NOT COMPLETED	518	513	396

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I (Placebo, Paclitaxel, Carboplatin) Control therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus placebo (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab) Bevacizumab-initiation therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Arm III (Paclitaxel, Carboplatin, Bevacizumab) Bevacizumab-throughout therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received bevacizumab, 15 mg/kg every 3 weeks.
Overall Study Disease Progression	309	274	195
Overall Study Patient Refusal	41	52	47
Overall Study Adverse Event	74	88	108
Overall Study Death	8	8	11
Overall Study Concomitant disease	3	2	4
Overall Study Other Reasons	79	88	27
Overall Study Did not receive study treatment	4	1	4

Baseline Characteristics

Carboplatin and Paclitaxel With or Without Bevacizumab in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Placebo, Paclitaxel, Carboplatin) n=625 Participants Control therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus placebo (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab) n=625 Participants Bevacizumab-initiation therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Arm III (Paclitaxel, Carboplatin, Bevacizumab) n=623 Participants Bevacizumab-throughout therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received bevacizumab, 15 mg/kg every 3 weeks.	Total n=1873 Participants Total of all reporting groups
Age, Continuous	59.3 years STANDARD_DEVIATION 10.9 • n=5 Participants	60.1 years STANDARD_DEVIATION 10.3 • n=7 Participants	59.7 years STANDARD_DEVIATION 10.6 • n=5 Participants	59.7 years STANDARD_DEVIATION 10.6 • n=4 Participants
Sex: Female, Male Female	625 Participants n=5 Participants	625 Participants n=7 Participants	623 Participants n=5 Participants	1873 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Non-Hispanic white	526 participant n=5 Participants	519 participant n=7 Participants	521 participant n=5 Participants	1566 participant n=4 Participants
Race/Ethnicity, Customized Asian	41 participant n=5 Participants	37 participant n=7 Participants	39 participant n=5 Participants	117 participant n=4 Participants
Race/Ethnicity, Customized Non-Hispanic black	25 participant n=5 Participants	28 participant n=7 Participants	27 participant n=5 Participants	80 participant n=4 Participants
Race/Ethnicity, Customized Hispanic	21 participant n=5 Participants	28 participant n=7 Participants	25 participant n=5 Participants	74 participant n=4 Participants
Race/Ethnicity, Customized Other or unspecified	12 participant n=5 Participants	13 participant n=7 Participants	11 participant n=5 Participants	36 participant n=4 Participants
Region of Enrollment United States	596 participants n=5 Participants	596 participants n=7 Participants	599 participants n=5 Participants	1791 participants n=4 Participants
Region of Enrollment Canada	1 participants n=5 Participants	5 participants n=7 Participants	3 participants n=5 Participants	9 participants n=4 Participants
Region of Enrollment Japan	21 participants n=5 Participants	12 participants n=7 Participants	12 participants n=5 Participants	45 participants n=4 Participants
Region of Enrollment Korea, Republic of	7 participants n=5 Participants	12 participants n=7 Participants	9 participants n=5 Participants	28 participants n=4 Participants
Gynecologic Oncology Group (GOG) Performance Status 0 - fully active	311 participants n=5 Participants	315 participants n=7 Participants	305 participants n=5 Participants	931 participants n=4 Participants
Gynecologic Oncology Group (GOG) Performance Status 1 - restricted strenuous activity, ambulatory	272 participants n=5 Participants	270 participants n=7 Participants	267 participants n=5 Participants	809 participants n=4 Participants
Gynecologic Oncology Group (GOG) Performance Status 2 - ambulatory, difficulty walking	42 participants n=5 Participants	40 participants n=7 Participants	51 participants n=5 Participants	133 participants n=4 Participants
Gynecologic Oncology Group (GOG) Performance Status 3 - limited self-care, partly confined to bed	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Gynecologic Oncology Group (GOG) Performance Status 4 - completely disabled, no self-care	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
International Federation of Gynecologic and Obstetrics (FIGO) Stage 1-limited to ovaries	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
International Federation of Gynecologic and Obstetrics (FIGO) Stage 1A-1 ovary involved, no ascites	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
International Federation of Gynecologic and Obstetrics (FIGO) Stage 1B-both ovaries involved, no ascites	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
International Federation of Gynecologic and Obstetrics (FIGO) Stage 1C-disease with capsules ruptured or ascites	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
International Federation of Gynecologic and Obstetrics (FIGO) Stage 2-disease with pelvic extension	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
International Federation of Gynecologic and Obstetrics (FIGO) Stage 2A-disease with extension to uterus and or tubes	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
International Federation of Gynecologic and Obstetrics (FIGO) Stage 2B-disease with extension to other pelvic tissues	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
International Federation of Gynecologic and Obstetrics (FIGO) Stage 2C-disease with capsules ruptured or ascites	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
International Federation of Gynecologic and Obstetrics (FIGO) Stage 3-disease w/ macroscopic implants outside pelvis	218 participants n=5 Participants	205 participants n=7 Participants	216 participants n=5 Participants	639 participants n=4 Participants
International Federation of Gynecologic and Obstetrics (FIGO) Stage 3-disease w/ implants > 1 cm outside pelvis	254 participants n=5 Participants	256 participants n=7 Participants	242 participants n=5 Participants	752 participants n=4 Participants
International Federation of Gynecologic and Obstetrics (FIGO) Stage 3A-disease w/ microscopic implants, negative nodes	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
International Federation of Gynecologic and Obstetrics (FIGO) Stage 3B-disease w/ abdominal implants <2cm, neg nodes	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
International Federation of Gynecologic and Obstetrics (FIGO) Stage 3C-disease w/ abdominal implants >2cm, pos nodes	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
International Federation of Gynecologic and Obstetrics (FIGO) Stage 4-distant metastatis	153 participants n=5 Participants	164 participants n=7 Participants	165 participants n=5 Participants	482 participants n=4 Participants
Histologic Type Serous adenocarcinoma	541 participants n=5 Participants	519 participants n=7 Participants	524 participants n=5 Participants	1584 participants n=4 Participants
Histologic Type Endometrioid	21 participants n=5 Participants	14 participants n=7 Participants	24 participants n=5 Participants	59 participants n=4 Participants
Histologic Type Clear cell	12 participants n=5 Participants	23 participants n=7 Participants	20 participants n=5 Participants	55 participants n=4 Participants
Histologic Type Mucinous	6 participants n=5 Participants	5 participants n=7 Participants	8 participants n=5 Participants	19 participants n=4 Participants
Histologic Type Other or not specified	45 participants n=5 Participants	64 participants n=7 Participants	47 participants n=5 Participants	156 participants n=4 Participants
Tumor Grade 3	445 participants n=5 Participants	465 participants n=7 Participants	460 participants n=5 Participants	1370 participants n=4 Participants
Tumor Grade 2	102 participants n=5 Participants	86 participants n=7 Participants	97 participants n=5 Participants	285 participants n=4 Participants
Tumor Grade 1	36 participants n=5 Participants	28 participants n=7 Participants	18 participants n=5 Participants	82 participants n=4 Participants
Tumor Grade Not graded	42 participants n=5 Participants	46 participants n=7 Participants	48 participants n=5 Participants	136 participants n=4 Participants

PRIMARY outcome

Timeframe: From study entry until first disease progression, death or date of last contact, up to 6 years

Median progression-free survival (PFS). Onset of progression could be based on radiographic (RECIST) criteria or rising CA-125 (GCIG criteria).

Outcome measures

Outcome measures
Measure	Arm I (Placebo, Paclitaxel, Carboplatin) n=625 Participants Control therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus placebo (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab) n=625 Participants Bevacizumab-initiation therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Arm III (Paclitaxel, Carboplatin, Bevacizumab) n=623 Participants Bevacizumab-throughout therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received bevacizumab, 15 mg/kg every 3 weeks.
Progression-free Survival	11.0 months Interval 10.2 to 12.0	12.3 months Interval 11.4 to 12.8	15.3 months Interval 14.2 to 16.1

SECONDARY outcome

Timeframe: From study entry to death or last contact, up to 6 years

Median overall survival (OS)

Outcome measures

Outcome measures
Measure	Arm I (Placebo, Paclitaxel, Carboplatin) n=625 Participants Control therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus placebo (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab) n=625 Participants Bevacizumab-initiation therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Arm III (Paclitaxel, Carboplatin, Bevacizumab) n=623 Participants Bevacizumab-throughout therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received bevacizumab, 15 mg/kg every 3 weeks.
Overall Survival	40.6 months Interval 37.1 to 45.5	38.7 months Interval 35.2 to 42.1	43.8 months Interval 39.7 to 49.0

SECONDARY outcome

Timeframe: Up to 5 years

Population: Eligible and evaluable patients

Eligible and Evaluable patients

Outcome measures

Outcome measures
Measure	Arm I (Placebo, Paclitaxel, Carboplatin) n=621 Participants Control therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus placebo (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab) n=624 Participants Bevacizumab-initiation therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Arm III (Paclitaxel, Carboplatin, Bevacizumab) n=619 Participants Bevacizumab-throughout therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received bevacizumab, 15 mg/kg every 3 weeks.
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Death, not CTC coded	5 Participants	8 Participants	10 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 White blood cell	317 Participants	328 Participants	327 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Absolute neutrophil count	540 Participants	543 Participants	536 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Hemoglobin	91 Participants	86 Participants	74 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Platelets	93 Participants	122 Participants	131 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Other hematologic	13 Participants	13 Participants	9 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Allergy/Immunology	23 Participants	25 Participants	14 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Auditory/Ear	1 Participants	1 Participants	2 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 hypertension	10 Participants	36 Participants	65 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Cardiac	14 Participants	12 Participants	18 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Coagulation	5 Participants	7 Participants	8 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Constitutional	62 Participants	61 Participants	83 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Dermatologic	13 Participants	20 Participants	16 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Endocrine	4 Participants	4 Participants	2 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Gastrointestinal	96 Participants	112 Participants	122 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Genitourinary/Renal	13 Participants	8 Participants	8 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Hemorrhage	5 Participants	9 Participants	15 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Hepatobiliary	2 Participants	1 Participants	3 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Infection	75 Participants	73 Participants	95 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Lymphatics	4 Participants	3 Participants	3 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Metabolic	91 Participants	87 Participants	101 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Musculoskeletal	16 Participants	17 Participants	21 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Neurosensory	23 Participants	26 Participants	28 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Other neurological	44 Participants	42 Participants	65 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Ocular/Visual	4 Participants	1 Participants	4 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Pain	74 Participants	82 Participants	101 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Pulmonary	29 Participants	36 Participants	32 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Vascular	37 Participants	33 Participants	40 Participants
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0 Sexual/Reproductive	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At baseline, 9, 18, 36, 60, and 84 weeks

Population: Number of valid QOL assessments do not total number of patients randomized in study.

Estimated least squares means from a mixed module of Quality of Life (QOL) scores at each assessment point, adjusted for baseline score and patient's age. Note: The range of possible scores of the FACT-O TOI is 0 - 104 for all treatment groups and at all visits. A higher score indicates better QOL. Baseline mean scores are raw means.

Outcome measures

Outcome measures
Measure	Arm I (Placebo, Paclitaxel, Carboplatin) n=625 Participants Control therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus placebo (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab) n=625 Participants Bevacizumab-initiation therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Arm III (Paclitaxel, Carboplatin, Bevacizumab) n=623 Participants Bevacizumab-throughout therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received bevacizumab, 15 mg/kg every 3 weeks.
Impact on Quality of Life Measured by the Functional Assessment of Cancer Therapy-Ovary Trial Outcome Index (FACT-O TOI) prior to treatment	68.2 units on a scale Standard Deviation 0.64	68.0 units on a scale Standard Deviation 0.66	67.4 units on a scale Standard Deviation 0.65
Impact on Quality of Life Measured by the Functional Assessment of Cancer Therapy-Ovary Trial Outcome Index (FACT-O TOI) prior to cycle 4	73.8 units on a scale Standard Deviation 0.53	71.1 units on a scale Standard Deviation 0.56	70.9 units on a scale Standard Deviation 0.54
Impact on Quality of Life Measured by the Functional Assessment of Cancer Therapy-Ovary Trial Outcome Index (FACT-O TOI) prior to cycle 7	76.0 units on a scale Standard Deviation 0.54	74.3 units on a scale Standard Deviation 0.56	73.8 units on a scale Standard Deviation 0.58
Impact on Quality of Life Measured by the Functional Assessment of Cancer Therapy-Ovary Trial Outcome Index (FACT-O TOI) prior to cycle 13	80.6 units on a scale Standard Deviation 0.62	80.5 units on a scale Standard Deviation 0.62	79.9 units on a scale Standard Deviation 0.58
Impact on Quality of Life Measured by the Functional Assessment of Cancer Therapy-Ovary Trial Outcome Index (FACT-O TOI) prior to cycle 21	77.6 units on a scale Standard Deviation 0.73	79.1 units on a scale Standard Deviation 0.71	78.6 units on a scale Standard Deviation 0.66
Impact on Quality of Life Measured by the Functional Assessment of Cancer Therapy-Ovary Trial Outcome Index (FACT-O TOI) 6 months followup	75.8 units on a scale Standard Deviation 0.78	77.6 units on a scale Standard Deviation 0.75	77.8 units on a scale Standard Deviation 0.75

Adverse Events

Arm I (Placebo, Paclitaxel, Carboplatin)

Serious events: 239 serious events

Other events: 589 other events

Deaths: 0 deaths

Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab)

Serious events: 257 serious events

Other events: 593 other events

Deaths: 0 deaths

Arm III (Paclitaxel, Carboplatin, Bevacizumab)

Serious events: 287 serious events

Other events: 588 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Melissa Leventhal

Gynecologic Oncology Group (GOG) Statistical and Data Center

Phone: 716-845-4030

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Arm I (Placebo, Paclitaxel, Carboplatin) n=621 participants at risk Control therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus placebo (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab) n=624 participants at risk Bevacizumab-initiation therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Arm III (Paclitaxel, Carboplatin, Bevacizumab) n=619 participants at risk Bevacizumab-throughout therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received bevacizumab, 15 mg/kg every 3 weeks.
Musculoskeletal and connective tissue disorders Soft Tissue Necrosis - Abdomen	0.16% 1/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Musculoskeletal and connective tissue disorders Joint-Function	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Musculoskeletal and connective tissue disorders Joint Effusion	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Musculoskeletal and connective tissue disorders Fracture	0.32% 2/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.48% 3/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.16% 1/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Immune system disorders Allergy/Immunology - Other	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Immune system disorders Allergic Reaction/Hypersensitivity	0.48% 3/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.96% 6/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.65% 4/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Blood and lymphatic system disorders Myelodysplasia	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Blood and lymphatic system disorders Neutrophils	2.3% 14/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	2.4% 15/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	2.1% 13/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Blood and lymphatic system disorders Platelets	0.16% 1/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.32% 2/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Blood and lymphatic system disorders Leukocytes	0.16% 1/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.32% 2/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.48% 3/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Blood and lymphatic system disorders Hemoglobin	0.48% 3/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.32% 2/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Cardiac disorders S/N Arrhythmia: Atrial Fibrillation	0.48% 3/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Cardiac disorders Cardiac Arrhythmia - Other	0.16% 1/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Cardiac disorders S/N Arrhythmia: Atrial Flutter	0.16% 1/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Cardiac disorders Vasovagal Episode	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Cardiac disorders Supraventricular Tachycardia	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.32% 2/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Cardiac disorders S/N Arrhythmia:supraventricular Nos	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Cardiac disorders S/N Arrhythmia: Sinus Bradycardia	0.16% 1/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Cardiac disorders Cardiac Ischemia/Infarction	0.32% 2/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.32% 2/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Cardiac disorders Hypertension	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.64% 4/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.81% 5/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Cardiac disorders Left Venticular Diastolic Dysfunction	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Cardiac disorders Cardiac General - Other	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Cardiac disorders Cardiac Troponin I (Ctni)	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Cardiac disorders Hypotension	0.16% 1/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.32% 2/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Vascular disorders Inr	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
General disorders Fever	0.48% 3/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.32% 2/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.81% 5/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
General disorders Fatigue	0.16% 1/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.64% 4/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.32% 2/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
General disorders Death No Ctcae Term - Disease Progression Nos	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.64% 4/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
General disorders Death No Ctcae Term - Death Nos	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.32% 2/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
General disorders Death No Ctcae Term - Multi-Organ Failure	0.16% 1/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
General disorders Death No Ctcae Term - Sudden Death	0.16% 1/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.32% 2/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.32% 2/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Skin and subcutaneous tissue disorders Wound Complication, Non-Infectious	0.48% 3/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.64% 4/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.65% 4/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Skin and subcutaneous tissue disorders Dermatology/Skin - Other	0.16% 1/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Skin and subcutaneous tissue disorders Ulceration	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Endocrine disorders Endocrine - Other	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Gastrointestinal disorders Fistula, Gi - Colon/Cecum/Appendix	0.16% 1/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.32% 2/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Gastrointestinal disorders Obstruction, Gi - Ileum	0.00% 0/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.00% 0/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	0.16% 1/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.

Other adverse events
Measure	Arm I (Placebo, Paclitaxel, Carboplatin) n=621 participants at risk Control therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus placebo (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab) n=624 participants at risk Bevacizumab-initiation therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Arm III (Paclitaxel, Carboplatin, Bevacizumab) n=619 participants at risk Bevacizumab-throughout therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received bevacizumab, 15 mg/kg every 3 weeks.
Immune system disorders Allergic Reaction/Hypersensitivity	9.0% 56/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	10.4% 65/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	11.0% 68/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Immune system disorders Rhinitis	10.8% 67/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	14.9% 93/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	15.8% 98/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Ear and labyrinth disorders Tinnitus	4.5% 28/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	2.9% 18/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	5.2% 32/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Blood and lymphatic system disorders Neutrophils	94.8% 589/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	94.7% 591/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	95.0% 588/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Blood and lymphatic system disorders Platelets	67.5% 419/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	68.3% 426/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	70.3% 435/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Blood and lymphatic system disorders Leukocytes	93.1% 578/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	95.0% 593/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	94.7% 586/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Blood and lymphatic system disorders Lymphopenia	5.3% 33/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	4.3% 27/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	5.2% 32/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Blood and lymphatic system disorders Hemoglobin	94.5% 587/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	92.0% 574/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	92.4% 572/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Cardiac disorders Palpitations	5.0% 31/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	3.5% 22/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	4.8% 30/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Cardiac disorders Hypertension	14.5% 90/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	23.9% 149/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	33.3% 206/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Cardiac disorders Hypotension	4.0% 25/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	4.0% 25/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	5.3% 33/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
General disorders Sweating	5.8% 36/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	5.9% 37/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	5.0% 31/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
General disorders Weight Gain	18.8% 117/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	17.0% 106/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	16.6% 103/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
General disorders Fever	9.8% 61/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	7.7% 48/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	12.0% 74/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
General disorders Weight Loss	12.2% 76/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	12.8% 80/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	16.3% 101/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
General disorders Rigors/Chills	5.8% 36/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	5.6% 35/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	6.9% 43/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
General disorders Fatigue	82.9% 515/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	82.9% 517/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	85.9% 532/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
General disorders Insomnia	20.1% 125/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	21.8% 136/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	21.6% 134/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Skin and subcutaneous tissue disorders Nail Changes	3.2% 20/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	4.6% 29/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	6.8% 42/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Skin and subcutaneous tissue disorders Hair Loss/Alopecia (Scalp Or Body)	72.8% 452/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	73.6% 459/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	71.7% 444/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Skin and subcutaneous tissue disorders Bruising	5.0% 31/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	5.0% 31/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	5.8% 36/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Skin and subcutaneous tissue disorders Rash	20.5% 127/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	19.7% 123/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	23.9% 148/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Skin and subcutaneous tissue disorders Dry Skin	5.6% 35/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	5.3% 33/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	5.8% 36/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Skin and subcutaneous tissue disorders Pruritus	9.2% 57/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	9.5% 59/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	10.7% 66/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Skin and subcutaneous tissue disorders Flushing	5.6% 35/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	5.3% 33/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	5.0% 31/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Skin and subcutaneous tissue disorders Dermatology/Skin - Other	6.0% 37/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	4.3% 27/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	5.3% 33/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Endocrine disorders Hot Flashes	16.1% 100/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	11.2% 70/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	15.7% 97/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Gastrointestinal disorders Heartburn	11.4% 71/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	12.2% 76/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	14.5% 90/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Gastrointestinal disorders Distention	8.5% 53/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	6.1% 38/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	5.8% 36/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Gastrointestinal disorders Taste Alteration	12.1% 75/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	11.2% 70/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	12.1% 75/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Gastrointestinal disorders Mucositis (Functional/Sympt) - Oral Cavity	9.3% 58/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	10.4% 65/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	16.6% 103/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Gastrointestinal disorders Mucositis (Clinical Exam) - Oral Cavity	9.2% 57/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	13.8% 86/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	15.7% 97/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Gastrointestinal disorders Vomiting	35.6% 221/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	34.6% 216/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	38.1% 236/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Gastrointestinal disorders Anorexia	29.6% 184/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	32.4% 202/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	32.6% 202/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Gastrointestinal disorders Dehydration	6.1% 38/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	9.9% 62/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	8.4% 52/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Gastrointestinal disorders Constipation	60.7% 377/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	56.2% 351/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	57.4% 355/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Gastrointestinal disorders Nausea	62.5% 388/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	63.9% 399/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	65.1% 403/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Gastrointestinal disorders Diarrhea	38.6% 240/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	42.5% 265/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	42.0% 260/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Vascular disorders Hemorrhage/Pulmonary - Nose	9.7% 60/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	29.0% 181/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	30.4% 188/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Infections and infestations Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos	6.1% 38/621 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	6.4% 40/624 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.	6.8% 42/619 • All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.