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.

Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: Final results of the randomized BEBYP trial / 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.. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - ELETTRONICO. - 26:(2015), pp. 724-730. [10.1093/annonc/mdv012]

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

Safina V.;Antonuzzo L.
Membro del Collaboration Group
;
Chiara S.;Bonetti A.
2015

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.
2015
26
724
730
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.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1193471
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