1302P - Clinical Impact of Presence and Type of Kras Mutation in a Population of EGFR Wild Type (WT) Advanced Non-Small Cell Lung Cancer (NSCLC) Patients (PTS) Treated with Platinum-Based Chemotherapy: A Retrospective Analysis

Abstract

ABSTRACT Background In this retrospective analysis we assessed whether KRAS mutation would affect the clinical outcome of EGFR WT advanced NSCLC pts treated with a first-line platinum-based chemotherapy. Moreover, the effect of specific mutant KRAS was evaluated. Methods One hundred and ninety-five EGFR WT, advanced NSCLC pts were included in the analysis. Study pts were treated at the Medical Oncology of the Perugia Hospital from Jan 2005 to March 2012. EGFR (exons 18 to 21) and KRAS (codons 12, 13 and 61) genes were amplified by nested PCR and sequenced in both sense and antisense directions. Results Median age was 60 years (29-81); 181 pts (92.8%) were PS 0 or 1; 155 pts (79.4%) belonged to the non-squamous subtype and 39 pts (20.0%) were never-smokers. Treatment was as follows: platinum + a third generation agent in 103 pts (52.8%); platinum + pemetrexed in 81 pts (41.6%); platinum-based doublet + bevacizumab in 11 pts (5.6%). Seventy-five pts (38.4%) were KRAS mutant (MUT), of which 60 pts at codon 12 (COD 12 MUT), 12 pts at codon 13 (COD 13 MUT) and 3 pts at codon 61 (COD 61 MUT). The most common amino acid changes found were: Gly12Cys (29 pts), Gly12Val (11 pts) and Gly13Cys (10 pts). In the whole study population, 69 pts (35.3%) responded to treatment and 62 pts (31.7%) achieved stable disease, for a disease control rate of 67.0%. At a median follow-up of 14 months (2-102), median progression-free survival (PFS) and overall survival (OS) were 6.2 and 21.6 months, respectively. When analyzed according to KRAS mutation status, a significantly shorter PFS was noted for the EGFR WT/KRAS MUT subgroup (n = 75) compared with the EGFR WT/KRAS WT population (n = 120) [5.1 vs 6.6 months, respectively, P = 0.02; HR = 1.43 (95% CI, 1.05 to 1.95)]. Similarly, a significant difference was observed between the two groups in terms of OS [13.7 vs 26.1 months, respectively, P = 0.02; HR = 1.56 (95% CI, 1.06 to 2.30)]. In the EGFR WT/KRAS MUT subrgoup, OS for COD 12 MUT, COD 13 MUT and COD 61 MUT was 17.2, 10.2 and 8.0 months, respectively, P = 0.17. Multivariate analysis for PFS and OS confirmed that KRAS mutation was an independent predictor of poorer oucome. Conclusions EGFR WT/KRAS MUT pts appear to experience a less favorable prognosis compared with the EGFR WT/KRAS WT genotype, with a significant difference in clinical outcome according to the mutant codon of KRAS. Disclosure All authors have declared no conflicts of interest.