Impact of Kras Mutation on the Response and Prognosis of Patients with Stage III Non-Squamous Non-Small Cell Lung Cancer

Abstract

ABSTRACT Aim: KRAS, a member of the RAS oncogene family, is known to be mutated at exon2 or exon3 in approximately 15%–30% of patients with advanced non-small cell lung cancer (NSCLC). The influence of mutated KRAS on the efficacy of chemotherapy or patient prognosis has been reported with some variability in magnitude, depending on the report. Notably, the influence of KRAS mutation in patients with potentially curable stage III NSCLC remains unknown. Methods: We evaluated the presence of KRAS mutations in consecutive non-squamous NSCLC patients who received chemoradiotherapy (CRT) between January 2001 and December 2010 at the National Cancer Center Hospital. The KRAS mutational analysis of exon2 (codon12 and codon13) was performed using a high-resolution melting analysis (HRMA). The response rate (RR), relapse-free survival (RFS), first relapse sites, survival post-progression (SPP), and overall survival (OS) were investigated according to the KRAS mutational status. Results: A total of 274 non-squamous NSCLC patients received CRT during the study period. Of these, sufficient specimens for mutational analysis could be obtained from 119 patients. Patients with KRAS mutations (Mt) were found at a frequency of 13% (16 out of 119). No significant differences in sex, age, smoking-index, clinical stage, or therapeutic regimens were observed between the Mt and wild-type KRAS (Wt) groups. The Mt group had a lower RR (63% vs. 81%) and a shorter median RFS (6.1 months vs. 10.9 months, P = 0.083). Regarding the first relapse sites, the Mt group had fewer local relapses (0% vs. 23%) and more brain metastases (46% vs. 12%). After disease relapse, the Mt group had a significantly shorter median SPP (2.5 months vs. 7.3 months, P = 0.028) and a shorter median OS (15.1 months vs. 29.1 months, P = 0.022). Conclusions: Among the stage III non-squamous NSCLC patients who received definitive CRT, 13% had KRAS mutations. The Mt group experienced more distant relapses (mainly in the brain) as their first relapses and had a significantly shorter survival time. Disclosure: All authors have declared no conflicts of interest.