TRIBE Trial: First-Line Treatment of mCRC

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Moderator, John L. Marshall, MD, introduces an in-depth panel discussion focused on the treatment of patients with metastatic colorectal cancer (mCRC). The exchange includes expert perspectives from a broad array of specialists, including Tanios Bekaii-Saab, MD, Fadi Braiteh, MD, CPI, Axel Grothey, MD, and Alan P. Venook, MD.

The conversation begins with a discussion of the recent phase III TRIBE trial, which was presented at the 2013 ASCO Annual Meeting. In this trial, FOLFOXIRI plus bevacizumab was compared to FOLFIRI plus bevacizumab as a first-line treatment for patients with mCRC. The primary endpoint of the trial was progression-free survival (PFS), although overall survival (OS) was also assessed, explains Axel Grothey, MD.

In total, 508 patients were enrolled in the trial. As expected, additional toxicity was observed with the FOLFOXIRI regimen; however, the levels of adverse events were tolerable, explains Grothey. In terms of efficacy, response rate was 64% compared to 53% for FOLFOXIRI and FOLFIRI, respectively. Furthermore, Grothey adds, the median PFS was 9.5 months with FOLFIRI versus 11.9 months with FOLFOXIRI (HR = 0.72).

Most impressively, Grothey believes, the median OS benefit for FOLFOXIRI plus bevacizumab was 31.0 months compared with 25.8 months in the FOLFIRI plus bevacizumab group (HR = 0.79, P = 0.054). At this point, the OS results are not statistically significant but will continue to be followed as the data matures. There were a few adjustments to the dosing for the FOFOXIRI regimen, notes Grothey. In this regimen, irinotecan was delivered at 180 mg/m2 ever 2 weeks compared to 165 mg/m2 with FOLFIRI.

A leading concern for the FOLFOXIRI plus bevacizumab regimen is that it deploys all effective therapies in the first-line setting leaving few new choices for second-line treatment, suggests Alan P. Venook, MD. To address this concern, the TRIBE trial administered the upfront regimen for 12 cycles (6 months) followed by 5-fluorouracil plus bevacizumab until progression. Following this approach, it may be acceptable to reintroduce irinotecan and oxaliplatin in the second-line setting, Grothey believes.