To the Editor:

In their article on the Triplet plus Bevacizumab (TRIBE) study, Loupakis et al. (Oct. 23 issue) conclude that chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab improved the outcome of patients with metastatic colorectal cancer, as compared with a control group receiving fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab. However, I question the basis for this conclusion.

First, although the median duration of progression-free survival was 12.1 months in the FOLFOXIRI group, as compared with 9.7 months in the control group, there was no significant improvement in overall survival with FOLFOXIRI. Second, FOLFOXIRI caused significantly more grade 3 or 4 events of neurotoxicity, diarrhea, neutropenia, and stomatitis, which are serious side effects. Third, even though tumors with nonmutated KRAS occurred in 37.3% of patients in the FOLFOXIRI group and 38.7% of those in the control group, subsequent treatment with an anti–epidermal growth factor receptor antibody (anti-EGFR) was performed in only 33% of patients in the FOLFOXIRI group and 29% of those in the control group, and the KRAS mutation status is not indicated for any of these patients. In addition, anti-EGFR was administered as second-line treatment in 31% of the patients in the FOLFOXIRI group, as compared with only 15% of the patients in the control group.

This study commenced around the same time that reports first appeared showing that in patients with advanced colorectal cancer with nonmutated KRAS who did not have a response to chemotherapy, cetuximab improved overall survival from 4.8 months to 9.5 months. It seems that this apparent imbalance in the use of proven effective follow-up treatment would make it difficult to properly compare the two treatment groups in the TRIBE study.

Ian E. Haines, F.R.A.C.P., F.A.Ch.P.M.
Monash University, Malvern, VIC, Australia

Source: The New England Journal of Medicine