A Randomized Phase III Study Evaluating the Continuation of Bevacizumab (BV) Beyond Progression in Metastatic Colorectal Cancer (MCRC) Patients (PTS) Who Received BV as Part of First-Line Treatment: Results of the Bebyp Trial by the Gruppo Oncologico Nord Ovest (GONO)

ABSTRACT Introduction Retrospective data suggested that the continuation of BV with second line chemotherapy (CT) beyond the progression to a first line treatment with BV was associated with improved survival. Methods This phase III study randomized pts with unresectable mCRC treated with BV plus first line CT (fluoropyrimidine, FOLFIRI, FOLFOX or FOLFOXIRI) to receive a second line CT with FOLFOX or FOLFIRI (depending on first-line chemotherapy) alone (arm A) or in combination with BV at 5 mg/Kg i.v. every 2 weeks (arm B). Pts were stratified according to center, PS (0 vs 1-2), disease free interval from the last administration of first line CT (≤3 months vs >3 months), second line regimen. The primary endpoint was progression-free survival (PFS). To detect a HR for PFS of 0.70 the trial was designed to randomize 262 pts. Considering that the AIO/AMG ML18147 trial with a similar design demonstrated an improved overall survival (OS) with BV beyond progression, the accrual was stopped on May 11th 2012. Results A total of 185 pts were randomized and 184 pts were included in the ITT analysis (1 pt randomized in error). Pts characteristics (arm A/arm B): number 92/92, gender M75%-F25%/M57%-F43%, median age 66 (38-75) years/62 (38-75) years, PS = 0 82%/82%, multiple site of disease 76%/77%, liver-only disease 15%/13%. The study met its primary endpoint. After a median follow up of 18 months the number of events for PFS was 172 (93%); median PFS was 4.97 months for arm A and 6.77 months for arm B (HR = 0.65; 95% CI 0.48–0.89; unstratified log-rank test, p = 0.0062). Adjusted analysis for PFS taking into account stratification factors, age and sex confirmed the increased PFS for arm B (HR = 0.70; 95% CI 0.50–0.97; p = 0.032). The response rate was 18% for CT and 21% for BEV + CT (p = 0.71). The OS data are still immature with a number of events of 52 in arm A and 46 in arm B. The adverse event profile was consistent with previously reported data for BEV + CT. Conclusions This study demonstrates an increased PFS by continuing BV in second-line. Updated results will be presented. Disclosure A. Falcone: Research grant from Amgen, Merck and Roche. All other authors have declared no conflicts of interest.