Trial Outcomes & Findings for A Study Evaluating the Efficacy and Safety of Bevacizumab in Combination With Chemotherapy in Untreated Metastatic Breast Cancer (RIBBON 1) (NCT NCT00262067)

NCT ID: NCT00262067

Last Updated: 2013-12-13

Results Overview

PFS was defined as the time from randomization to first documented disease progression (PD) as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) or death due to any cause, whichever occurred first. For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Target lesions should be selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements by imaging techniques or clinically. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions.

Recruitment status

UNKNOWN

Study phase

PHASE3

Target enrollment

1237 participants

Primary outcome timeframe

Baseline to the data cut-off date of 31 Jul 2008 (up to 2 years, 7 months)

Results posted on

2013-12-13

Participant Flow

Participant milestones

Participant milestones
Measure	Bevacizumab 15 mg/kg + Taxane or Anthracycline-based Regimen Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Taxane or Anthracycline-based Regimen Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Bevacizumab 15 mg/kg + Capecitabine Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Capecitabine Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.
Overall Study STARTED	415	207	409	206
Overall Study COMPLETED	196	107	193	93
Overall Study NOT COMPLETED	219	100	216	113

Reasons for withdrawal

Reasons for withdrawal
Measure	Bevacizumab 15 mg/kg + Taxane or Anthracycline-based Regimen Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Taxane or Anthracycline-based Regimen Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Bevacizumab 15 mg/kg + Capecitabine Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Capecitabine Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.
Overall Study Death	190	89	186	99
Overall Study Lost to Follow-up	5	4	7	5
Overall Study Sponsor's Decision to Terminate Study	1	0	0	0
Overall Study Patient Withdrew for Survival Follow-up	23	7	23	9

Baseline Characteristics

A Study Evaluating the Efficacy and Safety of Bevacizumab in Combination With Chemotherapy in Untreated Metastatic Breast Cancer (RIBBON 1)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bevacizumab 15 mg/kg + Taxane or Anthracycline-based Regimen n=415 Participants Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Taxane or Anthracycline-based Regimen n=207 Participants Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Bevacizumab 15 mg/kg + Capecitabine n=409 Participants Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Capecitabine n=206 Participants Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.	Total n=1237 Participants Total of all reporting groups
Age, Customized < 40 years	29 Participants n=5 Participants	14 Participants n=7 Participants	21 Participants n=5 Participants	15 Participants n=4 Participants	79 Participants n=21 Participants
Age, Customized 40-64 years	295 Participants n=5 Participants	160 Participants n=7 Participants	289 Participants n=5 Participants	137 Participants n=4 Participants	881 Participants n=21 Participants
Age, Customized ≥ 65 years	91 Participants n=5 Participants	33 Participants n=7 Participants	99 Participants n=5 Participants	54 Participants n=4 Participants	277 Participants n=21 Participants
Sex: Female, Male Female	413 Participants n=5 Participants	207 Participants n=7 Participants	408 Participants n=5 Participants	204 Participants n=4 Participants	1232 Participants n=21 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline to the data cut-off date of 31 Jul 2008 (up to 2 years, 7 months)

Population: Intent-to-treat population: All randomized patients, regardless of whether they received any study drug or completed the full course of treatment.

Outcome measures

Outcome measures
Measure	Bevacizumab 15 mg/kg + Taxane or Anthracycline-based Regimen n=415 Participants Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Taxane or Anthracycline-based Regimen n=207 Participants Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Bevacizumab 15 mg/kg + Capecitabine n=409 Participants Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Capecitabine n=206 Participants Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.
Progression-free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)	9.2 Months Interval 8.6 to 10.1	8.0 Months Interval 6.7 to 8.4	8.6 Months Interval 8.1 to 9.5	5.7 Months Interval 4.3 to 6.2

SECONDARY outcome

Timeframe: Baseline to the data cut-off date of 31 Jul 2008 (up to 2 years, 7 months)

Population: Intent-to-treat population: All randomized patients, regardless of whether they received any study drug or completed the full course of treatment. Only patients with measurable disease at baseline were included in the analysis.

An objective response was defined as a complete response or a partial response determined on two consecutive occasions ≥ 4 weeks apart as determined by the investigator using RECIST. For target lesions, a complete response was defined as the disappearance of all target lesions; a partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. For non-target lesions, a complete response was defined as the disappearance of all non-target lesions; a partial response was defined as the persistence of 1 or more non-target lesions.

Outcome measures

Outcome measures
Measure	Bevacizumab 15 mg/kg + Taxane or Anthracycline-based Regimen n=345 Participants Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Taxane or Anthracycline-based Regimen n=177 Participants Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Bevacizumab 15 mg/kg + Capecitabine n=325 Participants Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Capecitabine n=161 Participants Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.
Objective Response as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)	51.3 Percentage of participants Interval 45.9 to 56.7	37.9 Percentage of participants Interval 30.7 to 45.2	35.4 Percentage of participants Interval 30.2 to 40.6	23.6 Percentage of participants Interval 17.6 to 30.7

SECONDARY outcome

Timeframe: Baseline to the data cut-off date of 31 Jul 2008 (up to 2 years, 7 months)

Duration of objective response was defined as the time from the first tumor assessment that led to a determination of an objective response to the time of disease progression or death due to any cause, whichever occurred first.

Outcome measures

Outcome measures
Measure	Bevacizumab 15 mg/kg + Taxane or Anthracycline-based Regimen n=177 Participants Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Taxane or Anthracycline-based Regimen n=67 Participants Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Bevacizumab 15 mg/kg + Capecitabine n=115 Participants Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Capecitabine n=38 Participants Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.
Duration of Objective Response as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)	8.3 Months Interval 7.2 to 10.7	7.1 Months Interval 6.2 to 8.8	9.2 Months Interval 8.5 to 10.4	7.2 Months Interval 5.1 to 9.3

SECONDARY outcome

Timeframe: Baseline to the data cut-off of 23 Feb 2009 (up to 3 years, 2 months)

Population: Intent-to-treat population: All randomized patients, regardless of whether they received any study drug or completed the full course of treatment.

Overall survival was defined as the time from randomization until death from any cause.

Outcome measures

Outcome measures
Measure	Bevacizumab 15 mg/kg + Taxane or Anthracycline-based Regimen n=415 Participants Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Taxane or Anthracycline-based Regimen n=207 Participants Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Bevacizumab 15 mg/kg + Capecitabine n=409 Participants Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Capecitabine n=206 Participants Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.
Overall Survival	27.5 Months Interval 25.6 to 31.4	NA Months Interval 23.6 to The median and the upper limit of the confidence interval could not be estimated due to too few events.	25.7 Months Interval 22.0 to 28.4	22.8 Months Interval 20.5 to 28.4

SECONDARY outcome

Timeframe: Baseline to the data cut-off of 23 Feb 2009 (up to 3 years, 2 months)

Population: Intent-to-treat population: All randomized patients, regardless of whether they received any study drug or completed the full course of treatment.

1-year survival was defined as the percentage of patients who were alive 1 year after randomization. The percentage of patients alive at 1 year was determined using Kaplan-Meier analyses and the 95% confidence intervals were computed using the Brookmeyer-Crowley method.

Outcome measures

Outcome measures
Measure	Bevacizumab 15 mg/kg + Taxane or Anthracycline-based Regimen n=415 Participants Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Taxane or Anthracycline-based Regimen n=207 Participants Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Bevacizumab 15 mg/kg + Capecitabine n=409 Participants Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Capecitabine n=206 Participants Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.
1-year Survival	80.7 Percentage of participants Interval 76.8 to 84.5	83.2 Percentage of participants Interval 78.1 to 88.4	81.0 Percentage of participants Interval 77.1 to 84.8	74.8 Percentage of participants Interval 68.7 to 80.8

SECONDARY outcome

Timeframe: Baseline to the data cut-off date of 31 Jul 2008 (up to 2 years, 7 months)

Population: Intent-to-treat population: All randomized patients, regardless of whether they received any study drug or completed the full course of treatment.

PFS was defined as the time from randomization to first documented disease progression (PD) as determined by the Independent Review Committee using Response Evaluation Criteria in Solid Tumors (RECIST) or death due to any cause, whichever occurred first.

Outcome measures

Outcome measures
Measure	Bevacizumab 15 mg/kg + Taxane or Anthracycline-based Regimen n=415 Participants Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Taxane or Anthracycline-based Regimen n=207 Participants Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Bevacizumab 15 mg/kg + Capecitabine n=409 Participants Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Capecitabine n=206 Participants Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.
Progression-free Survival (PFS) as Determined by the Independent Review Committee Using Response Evaluation Criteria in Solid Tumors (RECIST)	10.7 Months Interval 9.9 to 12.1	8.3 Months Interval 8.0 to 9.9	9.8 Months Interval 8.4 to 10.4	6.2 Months Interval 4.7 to 7.8

Adverse Events

Bevacizumab 15 mg/kg + Taxane or Anthracycline-based Regimen

Serious events: 156 serious events

Other events: 91 other events

Deaths: 0 deaths

Placebo to Bevacizumab + Taxane or Anthracycline-based Regimen

Serious events: 59 serious events

Other events: 19 other events

Deaths: 0 deaths

Bevacizumab 15 mg/kg + Capecitabine

Serious events: 140 serious events

Other events: 72 other events

Deaths: 0 deaths

Placebo to Bevacizumab + Capecitabine

Serious events: 72 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Bevacizumab 15 mg/kg + Taxane or Anthracycline-based Regimen n=413 participants at risk Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Taxane or Anthracycline-based Regimen n=202 participants at risk Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + either a taxane or anthracycline-based standard chemotherapy for metastatic breast cancer.	Bevacizumab 15 mg/kg + Capecitabine n=404 participants at risk Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.	Placebo to Bevacizumab + Capecitabine n=201 participants at risk Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + capecitabine standard chemotherapy for metastatic breast cancer.
Blood and lymphatic system disorders Neutropenia	5.1% 21/413 • Adverse events were recorded from the first treatment until 30 days after the last treatment during the blinded treatment phase or the start date of the optional open-label treatment phase, whichever occurred first (up to 3 years 2 months). Safety population: All randomized patients who received any study treatment, defined as at least 1 full or partial dose of either study drug or chemotherapy. There were a total of 1220 patients in the safety population.	2.0% 4/202 • Adverse events were recorded from the first treatment until 30 days after the last treatment during the blinded treatment phase or the start date of the optional open-label treatment phase, whichever occurred first (up to 3 years 2 months). Safety population: All randomized patients who received any study treatment, defined as at least 1 full or partial dose of either study drug or chemotherapy. There were a total of 1220 patients in the safety population.	4.0% 16/404 • Adverse events were recorded from the first treatment until 30 days after the last treatment during the blinded treatment phase or the start date of the optional open-label treatment phase, whichever occurred first (up to 3 years 2 months). Safety population: All randomized patients who received any study treatment, defined as at least 1 full or partial dose of either study drug or chemotherapy. There were a total of 1220 patients in the safety population.	2.5% 5/201 • Adverse events were recorded from the first treatment until 30 days after the last treatment during the blinded treatment phase or the start date of the optional open-label treatment phase, whichever occurred first (up to 3 years 2 months). Safety population: All randomized patients who received any study treatment, defined as at least 1 full or partial dose of either study drug or chemotherapy. There were a total of 1220 patients in the safety population.
Cardiac disorders Left ventricular dysfunction	5.1% 21/413 • Adverse events were recorded from the first treatment until 30 days after the last treatment during the blinded treatment phase or the start date of the optional open-label treatment phase, whichever occurred first (up to 3 years 2 months). Safety population: All randomized patients who received any study treatment, defined as at least 1 full or partial dose of either study drug or chemotherapy. There were a total of 1220 patients in the safety population.	4.0% 8/202 • Adverse events were recorded from the first treatment until 30 days after the last treatment during the blinded treatment phase or the start date of the optional open-label treatment phase, whichever occurred first (up to 3 years 2 months). Safety population: All randomized patients who received any study treatment, defined as at least 1 full or partial dose of either study drug or chemotherapy. There were a total of 1220 patients in the safety population.	0.74% 3/404 • Adverse events were recorded from the first treatment until 30 days after the last treatment during the blinded treatment phase or the start date of the optional open-label treatment phase, whichever occurred first (up to 3 years 2 months). Safety population: All randomized patients who received any study treatment, defined as at least 1 full or partial dose of either study drug or chemotherapy. There were a total of 1220 patients in the safety population.	1.00% 2/201 • Adverse events were recorded from the first treatment until 30 days after the last treatment during the blinded treatment phase or the start date of the optional open-label treatment phase, whichever occurred first (up to 3 years 2 months). Safety population: All randomized patients who received any study treatment, defined as at least 1 full or partial dose of either study drug or chemotherapy. There were a total of 1220 patients in the safety population.
Renal and urinary disorders Proteinuria	5.3% 22/413 • Adverse events were recorded from the first treatment until 30 days after the last treatment during the blinded treatment phase or the start date of the optional open-label treatment phase, whichever occurred first (up to 3 years 2 months). Safety population: All randomized patients who received any study treatment, defined as at least 1 full or partial dose of either study drug or chemotherapy. There were a total of 1220 patients in the safety population.	0.50% 1/202 • Adverse events were recorded from the first treatment until 30 days after the last treatment during the blinded treatment phase or the start date of the optional open-label treatment phase, whichever occurred first (up to 3 years 2 months). Safety population: All randomized patients who received any study treatment, defined as at least 1 full or partial dose of either study drug or chemotherapy. There were a total of 1220 patients in the safety population.	3.2% 13/404 • Adverse events were recorded from the first treatment until 30 days after the last treatment during the blinded treatment phase or the start date of the optional open-label treatment phase, whichever occurred first (up to 3 years 2 months). Safety population: All randomized patients who received any study treatment, defined as at least 1 full or partial dose of either study drug or chemotherapy. There were a total of 1220 patients in the safety population.	0.00% 0/201 • Adverse events were recorded from the first treatment until 30 days after the last treatment during the blinded treatment phase or the start date of the optional open-label treatment phase, whichever occurred first (up to 3 years 2 months). Safety population: All randomized patients who received any study treatment, defined as at least 1 full or partial dose of either study drug or chemotherapy. There were a total of 1220 patients in the safety population.
Vascular disorders Hypertension	9.4% 39/413 • Adverse events were recorded from the first treatment until 30 days after the last treatment during the blinded treatment phase or the start date of the optional open-label treatment phase, whichever occurred first (up to 3 years 2 months). Safety population: All randomized patients who received any study treatment, defined as at least 1 full or partial dose of either study drug or chemotherapy. There were a total of 1220 patients in the safety population.	4.0% 8/202 • Adverse events were recorded from the first treatment until 30 days after the last treatment during the blinded treatment phase or the start date of the optional open-label treatment phase, whichever occurred first (up to 3 years 2 months). Safety population: All randomized patients who received any study treatment, defined as at least 1 full or partial dose of either study drug or chemotherapy. There were a total of 1220 patients in the safety population.	12.4% 50/404 • Adverse events were recorded from the first treatment until 30 days after the last treatment during the blinded treatment phase or the start date of the optional open-label treatment phase, whichever occurred first (up to 3 years 2 months). Safety population: All randomized patients who received any study treatment, defined as at least 1 full or partial dose of either study drug or chemotherapy. There were a total of 1220 patients in the safety population.	4.0% 8/201 • Adverse events were recorded from the first treatment until 30 days after the last treatment during the blinded treatment phase or the start date of the optional open-label treatment phase, whichever occurred first (up to 3 years 2 months). Safety population: All randomized patients who received any study treatment, defined as at least 1 full or partial dose of either study drug or chemotherapy. There were a total of 1220 patients in the safety population.

Additional Information

Medical Communications

Genentech, Inc.

Phone: 800 821-8590

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 only after the first publication or presentation that involves the Overall Study. The 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