Continuation of bevacizumab beyond progression improves outcome in patients with metastatic colorectal cancer
Results of the randomized BEBYP study
- Date: 01 Oct 2012
- Topic: Gastrointestinal cancers
A phase III study conducted by the Gruppo Oncologico Nord Ovest (Italy) evaluated whether continuing bevacizumab with second line chemotherapy beyond progression would improve survival in patients with unresectable metastatic colorectal cancer (mCRC), as suggested by retrospective data. The study results are reported by Dr G. Masi at the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna.
The trial randomized patients with mCRC who had received bevacizumab plus first line chemotherapy with fluoropyrimidine, FOLFIRI, FOLFOX or FOLFOXIRI to receive a second line of chemotherapy using either FOLFOX or FOLFIRI alone (arm A) or together with bevacizumab (arm B).
Patients were stratified according to center, performance status (PS 0 vs. 1-2), disease free interval from the last administration of first line chemotherapy (≤3 months vs. >3 months) and the second line regimen. The primary endpoint was progression-free survival (PFS). The trial was designed to randomize 262 patients but accrual was halted on May 11th 2012 when it was noted that the similarly designed AIO/AMG ML18147 trial showed improved overall survival (OS) with bevacizumab beyond progression.
Prior to the early end, the trial had randomized 185 patients; 184 patients were included in the intent to treat analysis since one patient had been randomized in error. Arm A comprised 92 patients who were 75% male with a median age of 66 years; 82% of patients had PS 0, 76% had disease at multiple sites and liver only disease was seen in 15% of patients. Patients in arm B were slightly younger with a median age of 62 but other characteristics were the same or similar to arm A.
The study met the primary endpoint; at median follow up of 18 months there were 172 (93%) events for PFS and median PFS was 4.97 months for arm A compared to 6.77 months for arm B, hazard ratio (HR) 0.65; p = 0.0062. A PFS analysis that adjusted for stratification factors, age and sex confirmed that bevacizumab added to chemotherapy improved PFS over chemotherapy alone, HR 0.70, p = 0.032.
An increased response was also demonstrated in arm B with response rates of 18% for chemotherapy alone and 21% for chemotherapy plus bevacizumab, but the difference was not statistically significant. Overall survival data are not yet mature with arm A having 52 events and arm B having 46 events thus far. The adverse event profile was consistent with previously reported data for bevacizumab plus chemotherapy.
In conclusion, continued bevacizumab plus second-line chemotherapy after progression to first-line therapy improves progression-free survival in patients with metastatic colorectal cancer.