Different Clinical Outcome of Metastatic Colorectal Cancer (MCRC) Patients Treated with Intensive Triplet Chemotherapy Plus Bevacizumab (FIR-B/FOX) According to Kras Genotype and Disease Extension

ABSTRACT Background Bevacizumab (BEV) plus triplet chemotherapy can increase efficacy of first-line treatment of MCRC (Bruera G et al, BMC Cancer 2010, 10:567), particularly if integrated with secondary liver surgery in liver-limited (L-L) patients (pts) (Bruera G et al, Clin Colorectal Cancer 2012). Clinical outcome of FIr-B/FOx regimen was evaluated according to KRAS genotype in L-L and other MCRC pts. Methods Tumoral and metastatic samples were screened for KRAS codon 12 and 13, and BRAF mutations by SNaPshot and/or direct sequencing. MCRC pts were classified as L-L and other or multiple metastatic (O/MM). Activity and efficacy were evaluated and compared using log-rank test. Results Fifty-nine pts were evaluated: 31 KRAS wild-type, 53%; 28 KRAS mutant, 47%. At 21.5 months median follow-up, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were, respectively: KRAS wild-type 90%, 14 months, 38 months; KRAS mutant 67%, 11 months, 20 months. PFS and OS were, respectively: overall in 25 L-L compared to 32 O/MM evaluable pts, 17 and 12 months, 47 and 21 months, significantly different; in KRAS wild-type, 12 L-L compared to 18 O/MM, 21 and 12 months, 47 and 28 months, significantly different; in KRAS mutant, 13 L-L compared to 14 O/MMS, 11 months equivalently, 39 and 19 months, not significantly different. Conclusion First line FIr-B/FOx regimen can increase activity and efficacy of KRAS wild-type and mutant MCRC pts; integration with secondary liver surgery significantly discriminates increased clinical outcome in KRAS wild-type L-L compared to O/MM pts while not in KRAS mutant pts. Disclosure All authors have declared no conflicts of interest.