P2.01-09 Targetable Genomic Alterations in KRAS Mutant Lung Adenocarcinoma by Targeted Next Generation Sequencing

Abstract

KRAS mutant (m) non-small cell lung cancer (NSCLC) represents 25% of cases. Despite the common mutation, biological and clinical behaviour of this disease is diverse. The aim of our study was to analyze co-occurring genomic alterations in advanced KRASm lung by next-generation sequencing (NGS) and compare them to a KRAS wild-type (WT) population. Advanced lung adenocarcinoma patients treated with a platinum doublet with KRAS mutation by Sanger were submitted to targeted NGS with the Oncomine Solid Tumor kit (DNA) and compared to a KRAS WT population of clinically similar patients. Association with outcome of the genomic alterations was evaluated. 32 KRASm patients and 18 WT patients were analyzed. The most frequent KRAS mutation was p.Gly12Cys (45%), followed by p.Gly12Val (24%). TP53 mutation was observed in 55% of KRASm tumors and 60% of WT cases (Table 1). Mutations in STK11 were found in 10% of cases in the KRAS mutant cohort while none in the WT. 3 out of the 4 cases of STK11 mutations coexisted with TP53 mutations. FGFR3, SMAD4 and DDR2 mutations were more frequently found in cases with KRAS mutations, although at low frequencies. Neither KRAS nor TP53 mutations had an impact in OS. We then selected the KRAS mutant cohort and evaluated the impact of co-mutations. TP53 or STK11 did not significantly affect OS of KRAS mutant patients. KRASm lung adenocarcinoma is genomically diverse. NGS provides biologically relevant information and druggable targets in this subset of patients.