Mutation in BRAF V600E—Reply

In Reply In reply to the comments of Emambux et al, we emphasize that our study population was restricted to patients with stage III colon carcinoma from 2 phase 3 FOLFOX-based adjuvant chemotherapy trials who experienced tumor recurrence. In patients with recurrence (n = 1395), we found that those whose cancers showed deficient mismatch repair (dMMR) and harbored BRAF V600E mutations had significantly worse survival after recurrence (SAR) compared with patients with dMMR tumors with nonmutated BRAF. This analysis was performed as a secondary aim, and we acknowledged that data for treatment after recurrence were not available and that patient numbers for these tumor subsets reflect their relatively low frequency despite 4979 participants in both trials. Our findings are supported by data in metastatic dMMR colorectal cancers in which mutated vs nonmutated BRAF was associated with significantly worse overall survival in a multivariable analysis. Furthermore, patients with stage III dMMR colon cancers and mutated BRAF had an increased rate of peritoneal recurrence that was associated with shorter time-to-recurrence and worse disease-free survival in the NCCTG N0147 trial.

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