Alternative metrics of response, such as early tumor shrinkage and depth of response, correlated with the overall survival benefit associated with FOLFIRI (5-fluorouracil, leucovorin, irinotecan) plus cetuximab, and with FOLFIRI plus bevacizumab, among patients with RAS wild-type metastatic colorectal cancer (mCRC), according to a study published in The Lancet Oncology.1

This FIRE-3 trial evaluated the efficacy and safety the 2 regimens among patients with KRAS exon 2 wild-type mCRC, including a subgroup of 400 patients with RAS wild-type disease.

In the RAS wild-type subgroup, FOLFIRI plus bevacizumab was associated with 30% reduction in the risk of death, in contrast with FOLFIRI plus cetuximab (hazard ratio, 0.70; 95% CI, 0.54-0.90; P = .0059). Investigator-assessed objective response and progression-free survival, however, were similar between the 2 treatment arms.

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Among the 330 CT-assessable patients with RAS wild-type mCRC, the proportion of patients achieving an objective response (P = .0029), frequency of early tumor shrinkage (P = .0005), and median depth of response (P < .0001) were better in those treated with FOLFIRI plus cetuximab.

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Early tumor shrinkage and depth of response, as assessed by centralized radiologic review, correlated with the overall survival benefit associated with either of the assessed therapies.

There were no differences in duration of response or time to response between the 2 groups.                


  1. Stintzing S, Modest DP, Rossius L, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumour dynamics in the final RAS wild-type subgroup of this randomised double-blind phase 3 trial. Lancet Oncol. 2016 Aug 26. doi: 10.1016/S1470-2045(16)30269-8 [Epub ahead of print]