FOLFOXIRI/bevacizumab (bev) versus FOLFIRI/bev as first-line treatment in unresectable metastatic colorectal cancer (mCRC) patients (pts): Results of the phase III TRIBE trial by GONO group.

Background: Doublets plus bev are a standard option for the first-line treatment of mCRC. First-line FOLFOXIRI demonstrated superior RR, PFS and OS compared to FOLFIRI. A phase II study of FOLFOXIRI/bev showed promising activity and manageable toxicities. The objective of the TRIBE trial was to confirm the superiority of FOLFOXIRI vs FOLFIRI when bev is added to chemotherapy (CT). Methods: Eligibility criteria included: measurable and unresectable mCRC, age 18-75 years, no prior CT for advanced disease. Pts were randomized to either FOLFIRI/bev (arm A) or FOLFOXIRI/bev (arm B). Both treatments were administered for a maximum of 12 cycles followed by 5FU/bev until progression. Primary endpoint was PFS. Results: Between July 2008 and May 2011 508 pts were randomized. Pts characteristics were (arm A/arm B): median age 60/61, ECOG PS 1-2 11%/10%, synchronous metastases 81%/79%, multiple sites of disease 74%/70%, liver-only disease 18%/23%, prior adjuvant (adj) 12%/12%. At a median follow-up of 26.6 mos 424 pts progressed and 244 died. Median PFS and OS in the intention to treat (ITT) population were 10.9 and 30.9 mos. FOLFOXIRI/bev significantly increased PFS (median 9.7 vs 12.2 mos, HR 0.73 [0.60-0.88] p=0.0012). Subgroup analyses based on stratification factors (PS, prior adj) and baseline characteristics (site of primary, liver only disease, resection of primary, Kohne score) did not evidence significant interactions between treatment and analyzed factors. A trend toward a more consistent effect of FOLFOXIRI/bev was reported in no prior adj (HR 0.68 [0.55-0.83]) compared to prior adj group (HR 1.18 [0.67-2.08], p for interaction=0.071). Response rate (RECIST) was also significantly improved (53% vs 65% p=0.006). FOLFOXIRI/bev did not increase the R0 secondary resection rate in the ITT population (12% vs 15%, p=0.327), or in the liver-only subgroup (28% vs 32%, p=0.823). Conclusions: FOLFOXIRI/bev compared to FOLFIRI/bev, significantly increases PFS and response rate. Subgroup analysis suggests a possible interaction between prior adj CT and PFS benefit. Secondary resection rate does not differ between treatment arms. Clinical trial information: NCT00719797