Background: Mutation (mut) of KRAS and BRAF negatively influence response to Cmab in metastatic colorectal cancer with the possible exception of KRAS Gly13Asp (JAMA 304:1812). Incidence of rash has served as a biomarker of a positive response to Cmab. N0147 assessed FOLFOX alone (arm A) or with Cmab (arm D) in resected stage III colon cancer. Impact of KRAS and BRAF mut status, and rash, on 3 yr DFS was assessed individually and jointly. Methods: Tissue from patients (pts) enrolled in N0147 was evaluated for mut in KRAS using the DxS mutation test kit KR-03/04 assessing for 7 different potential mut in codons 12 and 13. The V600E BRAF mut was assessed using an automated sequence technique. CTCAE v3.0 was used to classify and grade skin rash. Results: 2,580 pts were evaluable for KRAS analysis; 2516 for BRAF. See table for DFS based on KRAS and BRAF status. Pts with wtKRAS and wtBRAF had a DFS of 76% and 72% in arms A and D, respectively. 9% of pts treated with Cmab had Gr 3+ rash, with a nonsignificant trend toward increased DFS with rash in wtKRAS and wtBRAF groups (3 yr DFS in pts with rash 76% versus no rash 69%, p=0.26). Conclusions: Pts with wtKRAS and wtBRAF did not benefit from Cmab added to FOLFOX. None of the different KRAS mut predicted improved DFS with Cmab. DFS for pts with mutBRAF was similar to that for mutKRAS. Gr3+ rash was associated with some trend toward improved DFS with Cmab. Supported by NIH Grant CA25224, Bristol-Myers Squibb, ImClone, Sanofi-Aventis, and Pfizer.

Abbreviations: WT, wild-type; Mut, Mutation; HR, hazard ratio; CI, confidence interval.