For the treatment of metastatic colorectal cancer, better outcomes were achieved when bevacizumab (Avastin) was added to FOLFOXIRI (leucovorin, fluorouracil [5-FU], oxaliplatin, irinotecan), rather than FOLFIRI (leucovorin, 5-FU, irinotecan), in the phase III TRIBE trial conducted at 35 Italian centers and reported at the 2013 Gastrointestinal Cancers Symposium by Fotios Loupakis, MD, PhD, an oncologist at the Istituto Toscano Tumori in Pisa, Italy.

“The trial achieved its objective of confirming the superiority of FOLFOXIRI vs FOLFIRI in terms of progression-free survival, also in combination with bevacizumab,” Dr. Loupakis said. “FOLFOXIRI plus bevacizumab compared to FOLFIRI plus bevacizumab moderately increases specific side effects, but the overall safety profile is acceptable.”

Study Background

Dr. Loupakis noted that first-line FOLFOXIRI has demonstrated superior activity and efficacy compared to FOLFIRI in a previous phase III trial, while at the same time other studies showed that the addition of bevacizumab to first-line doublets improves outcomes. A phase II study of FOLFOXIRI plus bevacizumab, furthermore, showed promising activity and manageable toxicities.

The present Italian trial compared FOLFOXIRI/bevacizumab to FOLFIRI/bevacizumab as first-line treatment in 508 patients with unresectable metastatic colorectal cancer. The vast majority of the population had synchronous metastases and had more than one metastatic site (liver only was just about 20% in the two arms). Patients were randomly assigned to bevacizumab at 5 mg/kg plus either FOLFIRI or FOLFOXIRI.

Key Results

At a median follow-up of 26.6 months, FOLFOXIRI/bevacizumab reduced the risk of progression by 27% (P = .0012), a benefit consistently seen across all subgroups. Median progression-free survival was 12.2 vs 9.7 months.

The combination also increased response rate from 53% to 65% (P = .005). Cycles were delayed in 16% of the FOLFOXIRI group and 6% of the FOLFIRI arm, and there were slightly more dose reductions, “but these did not compromise the overall dose intensity of the treatment plan,” he noted.

The combination was, however, associated with more grade 3/4 diarrhea (19% vs 11%, P = .012), stomatitis (9% vs 4%, P = .048), and neutropenia (50% vs 20%, P < .001), but not febrile neutropenia, serious adverse events, treatment-related deaths, or early deaths. Serious adverse events were reported by approximately 20% in each arm.

Analyses of secondary resections, postprogression treatment, overall survival, and biomarkers are ongoing.

Conclusions

“Based on these results, we believe that FOLFOXIRI plus bevacizumab may represent a new option for the treatment of patients with metastatic colorectal cancer. We don’t think this is for all patients, but especially for patients selected according to the eligibility criteria of this study,” Dr. Loupakis said.

“Obviously, it will be important to see the overall survival data and the data in light of second-line treatments [an ongoing analysis],” Dr. Loupakis added. ■

Disclosure: Dr. Loupakis reported no potential conflicts of interest.

Reference

1. Loupakis F, Cremonlini C, Masi G et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of metastatic colorectal cancer: Results of the phase III randomized TRIBE trial. 2013 Gastrointestinal Cancers Symposium. Abstract 336. Presented January 26, 2013.