RIBBON-1

Randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer

Nicholas J. Robert, Véronique Diéras, John Glaspy, Adam M. Brufsky, Igor Bondarenko, Oleg N. Lipatov, Edith A. Perez, Denise A. Yardley, Stephen Y T Chan, Xian Zhou, See Chun Phan, Joyce O'Shaughnessy

Research output: Contribution to journalArticle

655 Citations (Scopus)

Abstract

Purpose: This phase III study compared the efficacy and safety of bevacizumab (BV) when combined with several standard chemotherapy regimens versus those regimens alone for first-line treatment of patients with human epidermal growth factor receptor 2-negative metastatic breast cancer. Patients and Methods: Patients were randomly assigned in 2:1 ratio to chemotherapy plus BV or chemotherapy plus placebo. Before random assignment, investigators chose capecitabine (Cape; 2,000 mg/m2 for 14 days), taxane (Tax) -based (nab-paclitaxel 260 mg/m2, docetaxel 75 or 100 mg/m2), or anthracycline (Anthra) -based (doxorubicin or epirubicin combinations [doxorubicin/cyclophosphamide, epirubicin/ cyclophosphamide, fluorouracil/epirubicin/cyclophosphamide, or fluorouracil/doxorubicin/ cyclophosphamide]) chemotherapy administered every 3 weeks. BV or placebo was administered at 15 mg/kg every 3 weeks. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), 1-year survival rate, objective response rate, duration of objective response, and safety. Two independently powered cohorts defined by the choice of chemotherapy (Cape patients or pooled Tax/Anthra patients) were analyzed in parallel. Results: RIBBON-1 (Regimens in Bevacizumab for Breast Oncology) enrolled 1,237 patients (Cape cohort, n = 615; Tax/Anthra cohort, n = 622). Median PFS was longer for each BV combination (Cape cohort: increased from 5.7 months to 8.6 months; hazard ratio [HR], 0.69; 95% CI, 0.56 to 0.84; log-rank P < .001; and Tax/Anthra cohort: increased from 8.0 months to 9.2 months; HR, 0.64; 95% CI, 0.52 to 0.80; log-rank P < .001). No statistically significant differences in OS between the placebo-and BV-containing arms were observed. Safety was consistent with results of prior BV trials. Conclusion: The combination of BV with Cape, Tax, or Anthra improves clinical benefit in terms of increased PFS in first-line treatment of metastatic breast cancer, with a safety profile comparable to prior phase III studies.

Original languageEnglish (US)
Pages (from-to)1252-1260
Number of pages9
JournalJournal of Clinical Oncology
Volume29
Issue number10
DOIs
StatePublished - Apr 1 2011
Externally publishedYes

Fingerprint

Placebos
Anthracyclines
Breast Neoplasms
Drug Therapy
Epirubicin
Cyclophosphamide
Disease-Free Survival
Safety
docetaxel
Therapeutics
Fluorouracil
Doxorubicin
Survival
Bevacizumab
human ERBB2 protein
Breast
Arm
Survival Rate
Research Personnel
taxane

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

RIBBON-1 : Randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. / Robert, Nicholas J.; Diéras, Véronique; Glaspy, John; Brufsky, Adam M.; Bondarenko, Igor; Lipatov, Oleg N.; Perez, Edith A.; Yardley, Denise A.; Chan, Stephen Y T; Zhou, Xian; Phan, See Chun; O'Shaughnessy, Joyce.

In: Journal of Clinical Oncology, Vol. 29, No. 10, 01.04.2011, p. 1252-1260.

Research output: Contribution to journalArticle

Robert, Nicholas J. ; Diéras, Véronique ; Glaspy, John ; Brufsky, Adam M. ; Bondarenko, Igor ; Lipatov, Oleg N. ; Perez, Edith A. ; Yardley, Denise A. ; Chan, Stephen Y T ; Zhou, Xian ; Phan, See Chun ; O'Shaughnessy, Joyce. / RIBBON-1 : Randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 10. pp. 1252-1260.
@article{ba726e243f29477ba869a2d5bceebfd2,
title = "RIBBON-1: Randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer",
abstract = "Purpose: This phase III study compared the efficacy and safety of bevacizumab (BV) when combined with several standard chemotherapy regimens versus those regimens alone for first-line treatment of patients with human epidermal growth factor receptor 2-negative metastatic breast cancer. Patients and Methods: Patients were randomly assigned in 2:1 ratio to chemotherapy plus BV or chemotherapy plus placebo. Before random assignment, investigators chose capecitabine (Cape; 2,000 mg/m2 for 14 days), taxane (Tax) -based (nab-paclitaxel 260 mg/m2, docetaxel 75 or 100 mg/m2), or anthracycline (Anthra) -based (doxorubicin or epirubicin combinations [doxorubicin/cyclophosphamide, epirubicin/ cyclophosphamide, fluorouracil/epirubicin/cyclophosphamide, or fluorouracil/doxorubicin/ cyclophosphamide]) chemotherapy administered every 3 weeks. BV or placebo was administered at 15 mg/kg every 3 weeks. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), 1-year survival rate, objective response rate, duration of objective response, and safety. Two independently powered cohorts defined by the choice of chemotherapy (Cape patients or pooled Tax/Anthra patients) were analyzed in parallel. Results: RIBBON-1 (Regimens in Bevacizumab for Breast Oncology) enrolled 1,237 patients (Cape cohort, n = 615; Tax/Anthra cohort, n = 622). Median PFS was longer for each BV combination (Cape cohort: increased from 5.7 months to 8.6 months; hazard ratio [HR], 0.69; 95{\%} CI, 0.56 to 0.84; log-rank P < .001; and Tax/Anthra cohort: increased from 8.0 months to 9.2 months; HR, 0.64; 95{\%} CI, 0.52 to 0.80; log-rank P < .001). No statistically significant differences in OS between the placebo-and BV-containing arms were observed. Safety was consistent with results of prior BV trials. Conclusion: The combination of BV with Cape, Tax, or Anthra improves clinical benefit in terms of increased PFS in first-line treatment of metastatic breast cancer, with a safety profile comparable to prior phase III studies.",
author = "Robert, {Nicholas J.} and V{\'e}ronique Di{\'e}ras and John Glaspy and Brufsky, {Adam M.} and Igor Bondarenko and Lipatov, {Oleg N.} and Perez, {Edith A.} and Yardley, {Denise A.} and Chan, {Stephen Y T} and Xian Zhou and Phan, {See Chun} and Joyce O'Shaughnessy",
year = "2011",
month = "4",
day = "1",
doi = "10.1200/JCO.2010.28.0982",
language = "English (US)",
volume = "29",
pages = "1252--1260",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "10",

}

TY - JOUR

T1 - RIBBON-1

T2 - Randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer

AU - Robert, Nicholas J.

AU - Diéras, Véronique

AU - Glaspy, John

AU - Brufsky, Adam M.

AU - Bondarenko, Igor

AU - Lipatov, Oleg N.

AU - Perez, Edith A.

AU - Yardley, Denise A.

AU - Chan, Stephen Y T

AU - Zhou, Xian

AU - Phan, See Chun

AU - O'Shaughnessy, Joyce

PY - 2011/4/1

Y1 - 2011/4/1

N2 - Purpose: This phase III study compared the efficacy and safety of bevacizumab (BV) when combined with several standard chemotherapy regimens versus those regimens alone for first-line treatment of patients with human epidermal growth factor receptor 2-negative metastatic breast cancer. Patients and Methods: Patients were randomly assigned in 2:1 ratio to chemotherapy plus BV or chemotherapy plus placebo. Before random assignment, investigators chose capecitabine (Cape; 2,000 mg/m2 for 14 days), taxane (Tax) -based (nab-paclitaxel 260 mg/m2, docetaxel 75 or 100 mg/m2), or anthracycline (Anthra) -based (doxorubicin or epirubicin combinations [doxorubicin/cyclophosphamide, epirubicin/ cyclophosphamide, fluorouracil/epirubicin/cyclophosphamide, or fluorouracil/doxorubicin/ cyclophosphamide]) chemotherapy administered every 3 weeks. BV or placebo was administered at 15 mg/kg every 3 weeks. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), 1-year survival rate, objective response rate, duration of objective response, and safety. Two independently powered cohorts defined by the choice of chemotherapy (Cape patients or pooled Tax/Anthra patients) were analyzed in parallel. Results: RIBBON-1 (Regimens in Bevacizumab for Breast Oncology) enrolled 1,237 patients (Cape cohort, n = 615; Tax/Anthra cohort, n = 622). Median PFS was longer for each BV combination (Cape cohort: increased from 5.7 months to 8.6 months; hazard ratio [HR], 0.69; 95% CI, 0.56 to 0.84; log-rank P < .001; and Tax/Anthra cohort: increased from 8.0 months to 9.2 months; HR, 0.64; 95% CI, 0.52 to 0.80; log-rank P < .001). No statistically significant differences in OS between the placebo-and BV-containing arms were observed. Safety was consistent with results of prior BV trials. Conclusion: The combination of BV with Cape, Tax, or Anthra improves clinical benefit in terms of increased PFS in first-line treatment of metastatic breast cancer, with a safety profile comparable to prior phase III studies.

AB - Purpose: This phase III study compared the efficacy and safety of bevacizumab (BV) when combined with several standard chemotherapy regimens versus those regimens alone for first-line treatment of patients with human epidermal growth factor receptor 2-negative metastatic breast cancer. Patients and Methods: Patients were randomly assigned in 2:1 ratio to chemotherapy plus BV or chemotherapy plus placebo. Before random assignment, investigators chose capecitabine (Cape; 2,000 mg/m2 for 14 days), taxane (Tax) -based (nab-paclitaxel 260 mg/m2, docetaxel 75 or 100 mg/m2), or anthracycline (Anthra) -based (doxorubicin or epirubicin combinations [doxorubicin/cyclophosphamide, epirubicin/ cyclophosphamide, fluorouracil/epirubicin/cyclophosphamide, or fluorouracil/doxorubicin/ cyclophosphamide]) chemotherapy administered every 3 weeks. BV or placebo was administered at 15 mg/kg every 3 weeks. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), 1-year survival rate, objective response rate, duration of objective response, and safety. Two independently powered cohorts defined by the choice of chemotherapy (Cape patients or pooled Tax/Anthra patients) were analyzed in parallel. Results: RIBBON-1 (Regimens in Bevacizumab for Breast Oncology) enrolled 1,237 patients (Cape cohort, n = 615; Tax/Anthra cohort, n = 622). Median PFS was longer for each BV combination (Cape cohort: increased from 5.7 months to 8.6 months; hazard ratio [HR], 0.69; 95% CI, 0.56 to 0.84; log-rank P < .001; and Tax/Anthra cohort: increased from 8.0 months to 9.2 months; HR, 0.64; 95% CI, 0.52 to 0.80; log-rank P < .001). No statistically significant differences in OS between the placebo-and BV-containing arms were observed. Safety was consistent with results of prior BV trials. Conclusion: The combination of BV with Cape, Tax, or Anthra improves clinical benefit in terms of increased PFS in first-line treatment of metastatic breast cancer, with a safety profile comparable to prior phase III studies.

UR - http://www.scopus.com/inward/record.url?scp=79953874259&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953874259&partnerID=8YFLogxK

U2 - 10.1200/JCO.2010.28.0982

DO - 10.1200/JCO.2010.28.0982

M3 - Article

VL - 29

SP - 1252

EP - 1260

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 10

ER -