Trial Outcomes & Findings for AURELIA: A Study of Avastin (Bevacizumab) Added to Chemotherapy in Patients With Platinum-resistant Ovarian Cancer (NCT NCT00976911)

Last Updated: 2022-06-21

Results Overview

Progression free survival was defined as the time from the date of randomization to the first documented disease progression or death, whichever occurs first. Progression was based on tumour assessment made by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (for participants with measurable disease), and for those with non-measurable disease presence or absence of lesions was noted.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

361 participants

Primary outcome timeframe

Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 14 November 2011

Results posted on

2022-06-21

Participant Flow

Participant milestones

Participant milestones
Measure	Chemotherapy Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 milligrams per square meter (mg/m\^2) as a 1-hour intravenous (IV) infusion on Days 1, 8, 15, and 22 every 4 weeks (q4w) OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 every 3 weeks \[q3w\]) OR pegylated liposomal doxorubicin (PLD) 40 mg/m\^2 as a 1 milligram per minute (mg/min) infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices.	Chemotherapy + Bevacizumab Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion. Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 milligrams per kilogram (mg/kg) IV every 2 weeks (q2w; or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m\^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
Overall Study STARTED	182	179
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	182	179

Reasons for withdrawal

Reasons for withdrawal
Measure	Chemotherapy Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 milligrams per square meter (mg/m\^2) as a 1-hour intravenous (IV) infusion on Days 1, 8, 15, and 22 every 4 weeks (q4w) OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 every 3 weeks \[q3w\]) OR pegylated liposomal doxorubicin (PLD) 40 mg/m\^2 as a 1 milligram per minute (mg/min) infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices.	Chemotherapy + Bevacizumab Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion. Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 milligrams per kilogram (mg/kg) IV every 2 weeks (q2w; or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m\^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
Overall Study Withdrawal by Subject	4	6
Overall Study Death	138	126
Overall Study Adverse Event	0	1
Overall Study Protocol Violation	2	0
Overall Study Other	8	9
Overall Study In Follow-Up as of 25 Jan 2013	30	37

Baseline Characteristics

AURELIA: A Study of Avastin (Bevacizumab) Added to Chemotherapy in Patients With Platinum-resistant Ovarian Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Chemotherapy n=182 Participants Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices.	Chemotherapy + Bevacizumab n=179 Participants Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 mg/kg IV q2w (or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m\^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.	Total n=361 Participants Total of all reporting groups
Age, Continuous	60.7 years STANDARD_DEVIATION 9.8 • n=5 Participants	60.0 years STANDARD_DEVIATION 11.1 • n=7 Participants	60.3 years STANDARD_DEVIATION 10.4 • n=5 Participants
Sex: Female, Male Female	182 Participants n=5 Participants	179 Participants n=7 Participants	361 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 14 November 2011

Population: ITT Population: All participants randomized to study treatment, irrespective of whether or not the assigned treatment was actually received. For all efficacy analyses, participants were grouped according to the treatment assigned at randomization

Outcome measures

Outcome measures
Measure	Chemotherapy n=182 Participants Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices.	Chemotherapy + Bevacizumab n=179 Participants Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 mg/kg IV q2w (or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m\^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
Percentage of Participants With Disease Progression or Death (Data Cutoff 14 November 2011)	92.3 percentage of participants	78.8 percentage of participants

PRIMARY outcome

Population: ITT Population; only participants with an event of progression or death were included in the analysis

PFS was defined as the time from the date of randomization to the first documented disease progression or death, whichever occurred first. Progression was based on tumor assessment made by the investigators according to the RECIST criteria (for participants with measurable disease), and for those with non-measurable disease presence or absence of lesions was noted. Time from randomization to occurrence of disease progression or death was measured in months. An event was defined as the earliest progressive disease or death that occurred on or before the cutoff date (14 November 2011), regardless of start of nonprotocol specified anti-cancer therapy or the bevacizumab monotherapy. Disease progression was assessed by investigator according to RECIST or by symptom deterioration, and could not be declared on the basis of rising cancer antigen 125 (CA125) levels alone. Kaplan-Meier methodology was used. 95% CI for median was computed using the method of Brookmeyer and Crowley.

Outcome measures

Outcome measures
Measure	Chemotherapy n=168 Participants Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices.	Chemotherapy + Bevacizumab n=141 Participants Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 mg/kg IV q2w (or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m\^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
Progression Free Survival (PFS; Data Cutoff 14 November 2011)	3.4 months Interval 2.1 to 3.75	6.8 months Interval 5.62 to 7.79

SECONDARY outcome

Population: ITT Population; only participants with measurable disease at baseline were included in the analysis.

Objective Response was determined by the investigator using modified RECIST criteria, Version 1.0. An objective response was a complete or partial overall confirmed response as determined by investigators. CR defined as complete disappearance of all target and non-target lesions and no new lesions. PR defined as greater than or equal to (≥) 30 percent (%) decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. 95% CI computed using the normal approximation to the binomial distribution.

Outcome measures

Outcome measures
Measure	Chemotherapy n=144 Participants Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices.	Chemotherapy + Bevacizumab n=142 Participants Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 mg/kg IV q2w (or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m\^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
Percentage of Participants With Best Overall Confirmed Objective Response of Complete Response (CR) or Partial Response (PR) Per Modified RECIST (Data Cutoff 14 November 2011)	12.5 percentage of participants Interval 7.1 to 17.9	28.2 percentage of participants Interval 20.8 to 35.6

SECONDARY outcome

Population: ITT Population; only participants with a best overall confirmed response of CR or PR were included in the analysis.

For randomized participants who achieved an objective response per modified RECIST, duration of objective response was defined as the time from the date of the first occurrence of a CR or PR (whichever occurred first) until the date that progressive disease or death was documented (whichever occurred first). Participants who had an objective response and did not experience disease progression or death by the time of analysis were censored at the time of the last tumor assessment. Summaries of duration of objective response (median and percentiles) were estimated from Kaplan-Meier curves. 95% CI for duration of objective response was computed using the method of Brookmeyer and Crowley.

Outcome measures

Outcome measures
Measure	Chemotherapy n=18 Participants Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices.	Chemotherapy + Bevacizumab n=40 Participants Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 mg/kg IV q2w (or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m\^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
Duration of Objective Response (Data Cutoff 14 November 2011)	5.4 months Interval 3.81 to 9.23	9.4 months Interval 6.6 to 11.63

SECONDARY outcome

Population: ITT Population

Outcome measures

Outcome measures
Measure	Chemotherapy n=182 Participants Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices.	Chemotherapy + Bevacizumab n=179 Participants Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 mg/kg IV q2w (or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m\^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
Percentage of Participants Who Died (Data Cutoff 25 January 2013)	75.8 percentage of participants	71.5 percentage of participants

SECONDARY outcome

Population: ITT Population; only participants who died were included in the analysis.

Duration of overall survival was defined as the time from randomization to death of any cause. Kaplan-Meier methodology was used. The OS data for participants for whom no death was captured in the clinical database were censored at the last time they were known to be alive. 95% CI was computed using the method of Brookmeyer and Crowley.

Outcome measures

Outcome measures
Measure	Chemotherapy n=138 Participants Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices.	Chemotherapy + Bevacizumab n=128 Participants Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 mg/kg IV q2w (or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m\^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
Overall Survival (Data Cutoff 25 January 2013)	13.3 months Interval 11.89 to 16.43	16.6 months Interval 13.7 to 18.99

SECONDARY outcome

Timeframe: Baseline and Weeks 8, 9, 16, 18, 24 and 30 (Data Cutoff 14 November 2011)

Population: ITT population; n (number) = (equals) number of participants that completed the questionnaire at baseline and at the specified visit.

The EORTC OV-28 module is a questionnaire that focuses on issues specific to ovarian cancer. It assesses AB/GI symptoms, among others. Participants were asked to indicate the extent to which they experienced AB/GI symptoms in the week prior to assessment. Participants responded on a scale of 1-4 (1=not at all, 2=a little, 3=quite a bit, 4=very much) to the following: Did you have abdominal pain? Did you have a bloated feeling in your abdomen/stomach? Did you have problems with your clothes feeling too tight? Did you experience any change in bowel habit as a result of your disease or treatment? Were you troubled by passing wind/gas/flatulence? Have you felt full too quickly after beginning to eat? Have you had indigestion/heartburn? Data are transformed to a scale from 0 to 100. Lower scores represent better health (fewer symptoms). Participants were considered a responder if they had a 10 point or more reduction in EORTC QLQ-OV28 AB/GI symptom scale score from baseline.

Outcome measures

Outcome measures
Measure	Chemotherapy n=84 Participants Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices.	Chemotherapy + Bevacizumab n=122 Participants Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 mg/kg IV q2w (or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m\^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Ovarian (OV) 28 Abdominal/Gastrointestinal (AB/GI) Symptom Scale - Percentage of Responders (Data Cutoff 14 November 2011) Week 30	33.3 percentage of participants Interval 9.9 to 65.1	28.6 percentage of participants Interval 15.7 to 44.6
European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Ovarian (OV) 28 Abdominal/Gastrointestinal (AB/GI) Symptom Scale - Percentage of Responders (Data Cutoff 14 November 2011) Weeks 8/9	19.0 percentage of participants Interval 11.3 to 29.1	27.9 percentage of participants Interval 20.1 to 36.7
European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Ovarian (OV) 28 Abdominal/Gastrointestinal (AB/GI) Symptom Scale - Percentage of Responders (Data Cutoff 14 November 2011) Weeks 16/18	23.3 percentage of participants Interval 11.8 to 38.6	26.7 percentage of participants Interval 17.8 to 37.4
European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Ovarian (OV) 28 Abdominal/Gastrointestinal (AB/GI) Symptom Scale - Percentage of Responders (Data Cutoff 14 November 2011) Week 24	22.7 percentage of participants Interval 7.8 to 45.4	32.1 percentage of participants Interval 19.9 to 46.3

Adverse Events

Chemotherapy

Serious events: 49 serious events

Other events: 129 other events

Deaths: 0 deaths

Chemotherapy + Bevacizumab

Serious events: 56 serious events

Other events: 146 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann- LaRoche

Phone: 1-800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but after the first publication or presentation that involves the overall study. Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Chemotherapy n=181 participants at risk Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices.	Chemotherapy + Bevacizumab n=179 participants at risk Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m\^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m\^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m\^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 mg/kg IV q2w (or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m\^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
Blood and lymphatic system disorders Anaemia	25.4% 46/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	19.6% 35/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Blood and lymphatic system disorders Leukopenia	13.8% 25/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	12.8% 23/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Blood and lymphatic system disorders Neutropenia	24.3% 44/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	30.7% 55/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Blood and lymphatic system disorders Thrombocytopenia	6.6% 12/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	5.6% 10/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Gastrointestinal disorders Abdominal pain	8.3% 15/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	9.5% 17/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Gastrointestinal disorders Abdominal pain upper	2.2% 4/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	5.0% 9/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Gastrointestinal disorders Constipation	9.4% 17/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	7.3% 13/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Gastrointestinal disorders Diarrhoea	5.5% 10/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	9.5% 17/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Gastrointestinal disorders Nausea	7.2% 13/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	9.5% 17/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Gastrointestinal disorders Vomiting	8.3% 15/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	7.8% 14/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
General disorders Fatigue	25.4% 46/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	27.4% 49/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
General disorders Mucosal inflammation	5.5% 10/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	12.8% 23/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Infections and infestations Infection	3.3% 6/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	10.6% 19/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Infections and infestations Urinary tract infection	7.2% 13/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	8.4% 15/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Investigations Weight decreased	2.8% 5/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	6.1% 11/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Metabolism and nutrition disorders Decreased appetite	7.7% 14/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	5.6% 10/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Nervous system disorders Peripheral sensory neuropathy	7.2% 13/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	17.9% 32/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Renal and urinary disorders Proteinuria	0.55% 1/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	12.3% 22/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.0% 9/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	5.6% 10/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	5.0% 9/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Skin and subcutaneous tissue disorders Alopecia	6.1% 11/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	8.4% 15/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	5.0% 9/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	10.6% 19/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.
Vascular disorders Hypertension	5.5% 10/181 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.	17.3% 31/179 • Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years). Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. The safety population included all treated participants.