Treatment beyond progression in metastatic colorectal cancer: to double or not to double the dose of bevacizumab?

Purpose: Bevacizumab or cetuximab represent the standard treatment in association with classical chemotherapy in confirmed metastatic colorectal cancer (mCRC). Bevacizumab could be continued after the first disease progression with an overall survival (OS) advantage, compared to chemotherapy alone, but the optimal dose remains a debatable issue. Methods: In a retrospective analysis of mCRC patients treated with bevacizumab, we selected patients with administration beyond progression, and stratified them according to the dose received- same dose bevacizumab (SDB) as first-line chemotherapy or double dose bevacizumab (DDB). For each group we evaluated OS, time to treatment failure (TTF) and progression-free survival in the first-line (PFS1) and in the second-line (PFS2). Results: In the first-line therapy, oxaliplatin backbone regimen was used in 73% SDB, compared with 22.5% DDB patients, while irinotecan was used in 75% DDB and 27% SDB patients. Second-line oxaliplatin was given to 50% DDB and 29.7% SDB patients, while irinotecan was administered to 47.5% DDB and 70.3% SDB patients. The median values were: OS - 41 months in the DDB group and 25 months in the SDB group (p = 0.01); TTF - 24 months in the DDB group and 19 months in the SDB group (p=0.009); PFSI 17 months in the DDB group and 12 months in the SDB group (p=0.008); PFS2 - 9 months in the DDB group and 5 months in the SDB group (p = 0.03). Conclusions: Doubling the dose of bevacizumab at progression seems to provide OS and PFS advantage for mCRC patients.