P-0270 Impact of Kras and Braf Gene Mutation Status on Outcomes of Chemotherapy in Combination with Bevacizumab in Metastatic Colorectal Cancer

ABSTRACT Introduction Mutations affecting KRAS are established predictive markers of outcome with anti-epithelial growth factor receptor antibodies, in metastatic colorectal cancer (mCRC). Several ongoing trials are investigated the predictive role of these and novel targeted agents in patients (pts) with BRAF mutation. The relevance of these biomarkers for anti-vascular endothelial growth factor therapy is still unclear. We aimed to evaluate the possible role of KRAS and BRAF status on therapeutic outcome and to assess the clinical response in different mCRC subgroup. Methods This was a retrospective study enrolling 67 pts treated with first-line FOLFIRI or FOLFOX chemotherapy plus bevacizumab. Tissue samples were analyzed for DNA sequencing to identify KRAS and BRAF mutations. Before therapy and after 3 months of treatment pts were investigated with CT scan. Mutation status was correlated with efficacy outcomes such as objective response rate (RR), mean progression-free survival (mPFS) and mean overall survival (mOS). Results KRAS and BRAF genes mutations were observed in 34.3% and 13.4% respectively. RR was available in all pts while mPFS and mOS in 63 pts. RR obtained in KRAS wild-type (wt) group was 54.5% vs 11.5% in KRAS mutated (mut) group, mPFS was 11.7 months vs 9.9 months respectively and mOS was 27.6 months vs 27.3 months. In BRAF wt group RR was 46.5% vs 22.2% in BRAF mut group. mPFS obtained in BRAF wt group was 11.4 months vs 7 months in BRAF mut group while mOS was 28.2 months vs 19.6 months. By analyzing RR, mPFS and mOS in the following subpopulations (40 pts KRAS wt/BRAF wt; 4 pts KRAS wt/BRAF mut; 18 pts KRAS mut/BRAF wt; 5 pts KRAS mut/BRAF mut) gave these results: in first subpopulation RR was 57.5%, mPFS 19.3 months and mOS 28.7 months; in second group RR 25%, mPFS 8 months, mOS 20.5 months; in KRAS mut/BRAF wt RR 22.2%, mPFS 10 months, mOS 27.5 months, finally in KRAS mut/BRAF mut RR 20%, mPFS 9.6 months, mOS 33 months. Also we evaluated the difference in RR, mPFS and mOS between KRAS wt/BRAF wt group and pts with a single or both oncogenes mutation. RR in pts with KRAS and BRAF wt was 57.5% vs 22.2% in pts with KRAS and/or BRAF mut; mPFS in the two groups was 19.3 months vs 7.9 months respectively and mOS was 28.7 months vs 21.9 months. Conclusion KRAS and BRAF oncogenes mutations were not clearly predictive of anti-vascular endothelial growth factor therapy outcome. Clinical response, mPFS and mOS in KRAS and BRAF groups were different with advantage in KRAS and BRAF wt groups. Also RR, mPFS and mOS tended to be higher in KRAS wt/BRAF wt group, while in pts with only one or both oncogenes mutation these values were lower.