Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: final results of the randomized BEBYP trial
Mené sur 185 patients atteints d'un cancer colorectal métastatique, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout du bevacizumab à une chimiothérapie mFOLFOX-6 ou FOLFIRI en traitement de deuxième ligne (durée médiane de suivi : 45,3 mois)
Background : The combination of bevacizumab with fluorouracil-based chemotherapy is a standard first-line treatment option in metastatic colorectal cancer. 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 metastatic colorectal cancer treated with fluoropyrimidine-based first-line chemotherapy plus bevacizumab were randomized to receive in second-line mFOLFOX-6 or FOLFIRI (depending on first-line regimen) with or without bevacizumab. The primary end-point was progression-free survival. To detect an 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, 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%CI 0.52-0.95; stratified log-rank p=0.010). Subgroup analyses showed a consistent benefit in all subgroups analysed 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 metastatic colorectal cancer.
Annals of Oncology 2015