Predictive and prognostic implications of KRAS genotype in patients with metastatic colorectal cancer (MCRC) treated with FIr-B/FOx association.

Abstract

457 Background: FIr-B/FOx association, consisting of triplet chemotherapy (FIr/FOx) plus bevacizumab, increases activity, efficacy, and resection rate of liver metastases in MCRC patients (Bruera G et al, submitted 2010). Even if bevacizumab-containing chemotherapy is also active in KRAS m MCRC patients, ORR, PFS, and OS seem to be lower compared to KRAS wt patients (Hurwitz et al, Oncologist 2009). Present data evaluates activity and efficacy of FIr-B/FOX according to KRAS genotype. Methods: Treatment schedule: weekly alternating bevacizumab (5 mg/kg days 1,15)/irinotecan (160 mg/m2) or oxaliplatin (80 mg/m2) associated to weekly 5- fluorouracil (12h-timed-flat-infusion, 900 mg/m2/d 1-2, 8-9, 15-16, 22-23); every 4 weeks. KRAS genotype was analyzed by direct sequencing or SNaPshot (Di Fiore et al, BJC'07) for KRAS codon 12 and 13 mutations. Results: Forty-two (84%) out of 50 enrolled patients (pts) in the FIr-B/FOx phase II study were evaluated: ORR 86% (C.I. ± 11), median PFS 13 months (3-46+), median OS 28 months (8-47). Liver metastasectomies (LM) were performed in 11 pts (26%): 42% of the 26 liver-MCRC pts; 58% of the 19 pts with liver-only MCRC pts. Twenty-five pts (59.5%) were KRAS wild-type (wt), 17 pts (40.5%) KRAS mutated (m). Clinical features were balanced. Among the 25 KRAS wt pts: ORR 88% (C.I. ± 14); median PFS 14 months (3-46+); median OS 31 months (8-47). LM were performed in 9 KRAS wt pts (36%): 56% of the 16 liver-MCRC pts; 82% of the 11 liver-only MCRC pts. Among the 17 KRAS m pts: ORR 82% (C.I. ± 19); median PFS 12 months (4-37+); median OS 19 months (8-44). LM were performed in 3 KRAS m pts (18%): 30% of the 10 liver-MCRC pts; 37.5% of the 8 liver-only MCRC pts. Conclusions: Triplet chemotherapy plus bevacizumab (FIr-B/FOx association) shows equivalent high activity (ORR) and efficacy (PFS) in KRAS wt and KRAS m MCRC pts; a trend toward a worse prognosis (OS) is confirmed in KRAS m pts. No significant financial relationships to disclose.