Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: Final results of the randomized BEBYP trial

Gianluca Masi, L. Salvatore, L. Boni, F. Loupakis, C. Cremolini, L. Fornaro, M. Schirripa, S. Cupini, C. Barbara, V. Safina, C. Granetto, E. Fea, L. Antonuzzo, C. Boni, G. Allegrini, S. Chiara, D. Amoroso, A. Bonetti

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Abstract

Background: The combination of bevacizumab with fluorouracil-based chemotherapy is a standard first-line treatment option in metastatic colorectal cancer (mCRC). We studied the efficacy of continuing or reintroducing bevacizumab in combination with second-line chemotherapy after progression to bevacizumab-based first-line therapy. Patients and methods: In this phase III study, patients with mCRC treated with fluoropyrimidine-based first-line chemotherapy plus bevacizumab were randomized to receive in second-line mFOLFOX-6 or FOLFIRI (depending on firstline regimen) with or without bevacizumab. The primary end point was progression-free survival. To detect a hazard ratio (HR) for progression of 0.70 with an α and β error of 0.05 and 0.20, respectively, 262 patients were required. Results: In consideration of the results of the ML18147 trial, the study was prematurely stopped. Between April 2008 and May 2012, a total of 185 patients were randomized. Bevacizumab-free interval was longer than 3 months in 43% of patients in chemotherapy alone arm and in 50% of patients in the bevacizumab arm. At a median follow-up of 45.3 months, the median progression-free survival was 5.0 months in the chemotherapy group and 6.8 months in the bevacizumab group [adjusted HR = 0.70; 95% confidence interval (CI) 0.52-0.95; stratified log-rank P = 0.010]. Subgroup analyses showed a consistent benefit in all subgroups analyzed and in particular in patients who had continued or reintroduced bevacizumab. An improved overall survival was also observed in the bevacizumab arm (adjusted HR = 0.77; 95% CI 0.56-1.06; stratified log-rank P = 0.043). Responses (RECIST 1.0) were similar in the chemotherapy and bevacizumab groups (17% and 21%; P = 0.573). Toxicity profile was consistent with previously reported data. Conclusions: This study demonstrates that the continuation or the reintroduction of bevacizumab with second-line chemotherapy beyond first progression improves the outcome and supports the use of this strategy in the treatment of mCRC. Clinical Trials.gov number: NCT00720512.

Original languageEnglish
Pages (from-to)724-730
Number of pages7
JournalAnnals of Oncology
Volume26
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

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Colorectal Neoplasms
Drug Therapy
Therapeutics
Disease-Free Survival
Bevacizumab
Confidence Intervals
Fluorouracil
Clinical Trials
Survival

Keywords

  • Bevacizumab
  • Beyond progression
  • Metastatic colorectal cancer
  • Second-line

ASJC Scopus subject areas

  • Oncology
  • Hematology
  • Medicine(all)

Cite this

Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer : Final results of the randomized BEBYP trial. / Masi, Gianluca; Salvatore, L.; Boni, L.; Loupakis, F.; Cremolini, C.; Fornaro, L.; Schirripa, M.; Cupini, S.; Barbara, C.; Safina, V.; Granetto, C.; Fea, E.; Antonuzzo, L.; Boni, C.; Allegrini, G.; Chiara, S.; Amoroso, D.; Bonetti, A.

In: Annals of Oncology, Vol. 26, No. 4, 01.04.2015, p. 724-730.

Research output: Contribution to journalArticle

Masi, G, Salvatore, L, Boni, L, Loupakis, F, Cremolini, C, Fornaro, L, Schirripa, M, Cupini, S, Barbara, C, Safina, V, Granetto, C, Fea, E, Antonuzzo, L, Boni, C, Allegrini, G, Chiara, S, Amoroso, D & Bonetti, A 2015, 'Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: Final results of the randomized BEBYP trial', Annals of Oncology, vol. 26, no. 4, pp. 724-730. https://doi.org/10.1093/annonc/mdv012
Masi, Gianluca ; Salvatore, L. ; Boni, L. ; Loupakis, F. ; Cremolini, C. ; Fornaro, L. ; Schirripa, M. ; Cupini, S. ; Barbara, C. ; Safina, V. ; Granetto, C. ; Fea, E. ; Antonuzzo, L. ; Boni, C. ; Allegrini, G. ; Chiara, S. ; Amoroso, D. ; Bonetti, A. / Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer : Final results of the randomized BEBYP trial. In: Annals of Oncology. 2015 ; Vol. 26, No. 4. pp. 724-730.
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T2 - Final results of the randomized BEBYP trial

AU - Masi, Gianluca

AU - Salvatore, L.

AU - Boni, L.

AU - Loupakis, F.

AU - Cremolini, C.

AU - Fornaro, L.

AU - Schirripa, M.

AU - Cupini, S.

AU - Barbara, C.

AU - Safina, V.

AU - Granetto, C.

AU - Fea, E.

AU - Antonuzzo, L.

AU - Boni, C.

AU - Allegrini, G.

AU - Chiara, S.

AU - Amoroso, D.

AU - Bonetti, A.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Background: The combination of bevacizumab with fluorouracil-based chemotherapy is a standard first-line treatment option in metastatic colorectal cancer (mCRC). We studied the efficacy of continuing or reintroducing bevacizumab in combination with second-line chemotherapy after progression to bevacizumab-based first-line therapy. Patients and methods: In this phase III study, patients with mCRC treated with fluoropyrimidine-based first-line chemotherapy plus bevacizumab were randomized to receive in second-line mFOLFOX-6 or FOLFIRI (depending on firstline regimen) with or without bevacizumab. The primary end point was progression-free survival. To detect a hazard ratio (HR) for progression of 0.70 with an α and β error of 0.05 and 0.20, respectively, 262 patients were required. Results: In consideration of the results of the ML18147 trial, the study was prematurely stopped. Between April 2008 and May 2012, a total of 185 patients were randomized. Bevacizumab-free interval was longer than 3 months in 43% of patients in chemotherapy alone arm and in 50% of patients in the bevacizumab arm. At a median follow-up of 45.3 months, the median progression-free survival was 5.0 months in the chemotherapy group and 6.8 months in the bevacizumab group [adjusted HR = 0.70; 95% confidence interval (CI) 0.52-0.95; stratified log-rank P = 0.010]. Subgroup analyses showed a consistent benefit in all subgroups analyzed and in particular in patients who had continued or reintroduced bevacizumab. An improved overall survival was also observed in the bevacizumab arm (adjusted HR = 0.77; 95% CI 0.56-1.06; stratified log-rank P = 0.043). Responses (RECIST 1.0) were similar in the chemotherapy and bevacizumab groups (17% and 21%; P = 0.573). Toxicity profile was consistent with previously reported data. Conclusions: This study demonstrates that the continuation or the reintroduction of bevacizumab with second-line chemotherapy beyond first progression improves the outcome and supports the use of this strategy in the treatment of mCRC. Clinical Trials.gov number: NCT00720512.

AB - Background: The combination of bevacizumab with fluorouracil-based chemotherapy is a standard first-line treatment option in metastatic colorectal cancer (mCRC). We studied the efficacy of continuing or reintroducing bevacizumab in combination with second-line chemotherapy after progression to bevacizumab-based first-line therapy. Patients and methods: In this phase III study, patients with mCRC treated with fluoropyrimidine-based first-line chemotherapy plus bevacizumab were randomized to receive in second-line mFOLFOX-6 or FOLFIRI (depending on firstline regimen) with or without bevacizumab. The primary end point was progression-free survival. To detect a hazard ratio (HR) for progression of 0.70 with an α and β error of 0.05 and 0.20, respectively, 262 patients were required. Results: In consideration of the results of the ML18147 trial, the study was prematurely stopped. Between April 2008 and May 2012, a total of 185 patients were randomized. Bevacizumab-free interval was longer than 3 months in 43% of patients in chemotherapy alone arm and in 50% of patients in the bevacizumab arm. At a median follow-up of 45.3 months, the median progression-free survival was 5.0 months in the chemotherapy group and 6.8 months in the bevacizumab group [adjusted HR = 0.70; 95% confidence interval (CI) 0.52-0.95; stratified log-rank P = 0.010]. Subgroup analyses showed a consistent benefit in all subgroups analyzed and in particular in patients who had continued or reintroduced bevacizumab. An improved overall survival was also observed in the bevacizumab arm (adjusted HR = 0.77; 95% CI 0.56-1.06; stratified log-rank P = 0.043). Responses (RECIST 1.0) were similar in the chemotherapy and bevacizumab groups (17% and 21%; P = 0.573). Toxicity profile was consistent with previously reported data. Conclusions: This study demonstrates that the continuation or the reintroduction of bevacizumab with second-line chemotherapy beyond first progression improves the outcome and supports the use of this strategy in the treatment of mCRC. Clinical Trials.gov number: NCT00720512.

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