Correlation of KRAS status with clinical outcome in patients (pts) with metastatic colorectal cancer (mCRC) treated first-line with FOLFOX6 + cetuximab (FX+C) or FOLFIRI + cetuximab (FF+C): The CECOG/CORE1.2.001 trial

Abstract

4055 Background: Previous retrospective analyses of KRAS mutation status from the randomized CECOG/CORE 1.2.001 phase II trial has shown that treatment with cetuximab plus standard chemotherapy (CT) in pts with KRAS wild-type (wt) tumors leads to significantly better progression-free survival (PFS) and overall survival (OS) compared with KRAS mutant (mt) tumors. Methods: CECOG investigators performed a post-study survival update, re-assessing the impact of KRAS status and other possible predictive factors for OS using multivariable Cox proportional hazard methods. Results: KRAS-evaluable tissue was available from 117 (77%) of 151 pts in the ITT population. KRAS wt status was detected in 53% (n=62) of tumors (34/57 and 28/60 in the FX+C and FF+C arm, respectively). After a median follow up of 29 months (mo), OS in pts with KRAS wt tumors was significantly improved compared to pts with KRAS mt tumors (median 20.8 vs 15.9 mo; hazard ratio (HR)=1.62; p=0.0296). OS analysis by treatment arm revealed a statistically significant difference in favor of pts with KRAS wt tumors in the FX+C arm (median 22.5 vs 15.2; HR=2.06; p=0.0201) and no significant differences in the FF+C arm. Exploratory multivariable Cox proportional hazard analysis showed that as well as KRAS wt status (vs KRAS mt), an acne-like rash of grade 2/3 (vs grade 0/1) in the first 6 weeks and no prior treatment (vs prior neo-/adjuvant treatment) were the strongest independent predictors for prolonged survival (each p<0.005). Conclusions: This analysis confirmed the results of previous studies: treatment with cetuximab plus standard CT in pts with KRAS wt tumors leads to significantly better OS compared to pts with KRAS mt tumors. The early occurrence of a cetuximab-related grade 2/3 acne-like rash seems to be an independent predictor for prolonged survival in addition to KRAS status. The relevance of the lower predictive value of KRAS status noted for OS in the FF+C arm pts vs the significant effect in the FX+C arm is undetermined due to the low sample size of the subgroup analyses. [Table: see text]