RESUMO
BACKGROUND: The addition of bevacizumab (BEV) to standard doublet chemotherapy improves outcomes compared with chemotherapy alone in patients with metastatic colorectal cancer (mCRC). The OPAL study examined the effect of BEV+FOLFOXIRI followed by 5FU/LV and BEV maintenance on progression-free survival (PFS) in patients with previously untreated unresectable mCRC. METHODS: Eligible patients had histologically confirmed mCRC, ECOG performance status ⩽1 and were 18-70 years old. Patients received up to 12 cycles of FOLFOXIRI+BEV q2w (induction phase) followed by up to ⩽40 cycles of 5FU/LV+BEV q2w (maintenance phase). Median PFS was the primary end point; secondary end points included response, OS, secondary resection rate, safety and prognostic value of pharmacogenetic profiling. RESULTS: Ninety-seven patients were enrolled. Of these, 90 received study medication and formed the safety population: 64 males; median age 58 (range 28-71) years; ECOG performance status 0/1 in 54%/46% patients; and liver only disease in 35 patients. Relative dose intensities were 79-85% for all four drugs. The incidence of adverse events (AEs) was as previously reported and there were no new safety signals. In total, 87 serious AEs occurred in 39 patients (43%). Median PFS was 11.1 months (95% CI 9.4-12.0) and did thus not meet the primary objective of 12 months. Median OS was 32.2 months (95% CI 22.6-36.9). Fifty-two patients were pharmacogenetically profiled. CONCLUSIONS: FOLFOXIRI+BEV was feasible in this molecularly unselected mCRC patient population, showing a high efficacy in terms of survival, overall response and secondary resection rate. Pharmacogenomic profiling revealed no clinically relevant marker.