P-0257 Bevacizumab Effectiveness in First-Line Treatment of Metastatic Colorectal Cancer, in Relation to Kras Expression and Metastatic Sites

Abstract

ABSTRACT Introduction Bevacizumab (BEV) combined with chemotherapy prolongs PFS and OS in metastatic colorectal cancer (mCRC) independently of KRAS status. This study investigated the role of anti-vascular endothelial growth factor therapy on clinical response, mean progression-free survival (mPFS) and mean overall survival (mOS) according to KRAS status and metastatic sites. Methods 108 patients (pts) were treated with first-line FOLFIRI or FOLFOX chemotherapy in combination with BEV. Tissue samples were analyzed for DNA sequencing to identify KRAS mutations. Before therapy and after 3 months of chemotherapy pts were investigated with CT scan. Statistical association was evaluated by chi-square test and logistic regression analysis to objective response rate (RR). Results RR was available in 108 pts while mPFS and mOS in 106 pts. Overall, 45 (41.7%) pts had a stable disease, 43 (39.8%) showed a partial response, 4 (3,7%) complete response and 16 (14.8%) disease progression, accounting for RR of 43.5%. mPFS was 11.3 months and mOS was 26.9 months. 53 pts presented only hepatic metastases. RR was higher in pts with only hepatic metastasis as compared to those with extra-hepatic or multiple metastases, although the difference failed to reach a statistical significant (49% vs 39%; HR: 1.23; 95% CI: 0.79 – 1.90; p=0.36). In pts with only hepatic metastases mPFS was 12 months vs 11 months in pts with multiple metastatic sites or extra-hepatic metastases, while mOS was 24.8 months vs 27.1 months respectively. KRAS mutations were investigated in 108 patients. 69 patients were wild-type (wt 64%) while 39 patients were mutated ( mut 36%). RR was 49.3% in wt group vs 33,3% in mut group (HR: 0,51; 95% CI: 0,23 - 1,16; p=0.11), mPFS was 12.8 months in KRAS wt group vs 10 months in KRAS mut group and mOS was 28.8 months vs 23.9 months respectively. Conclusion RR in KRAS groups was different with an advantage in KRAS wt, but this difference was not statistical significant. mPFS and mOS tended to be higher in KRAS wt pts. There was evidence of not statistical significant advantage, in terms of clinical response to treatment with Bevacizumab, in pts with only hepatic metastases. Therefore in this subset of pts a favorable trend was demonstrated. Unfortunately, despite positive trend, an increase in mPFS and mOS compared to pts with extra-hepatic metastases or multiple metastatic sites was not shown.