P86.18 Prevalence, Clinical Characteristics and Survival of Patients with KRAS Mutant Lung Cancer in Argentina.

Abstract

Between 20-35% of lung adenocarcinomas harbor a KRAS gene mutations (KRASm), most commonly in codon 12. With the development of KRAS G12C covalent inhibitors as novel targeted therapies in this population, there is renewed interest in understanding the clinical features and outcomes of patients with KRAS mutant non-small cell lung cancer (NSCLC) worldwide. Clinical and pathologic data were collected for patients with KRAS mutant lung cancer in two academic hospital, CEMIC and Hospital Italiano de Buenos Aires (HIBA) in Argentina. Molecular profiling of tumor samples was done in a cohort of patients using targeted next generation sequencing (NGS) with Oncomine Focus Assay (ThermoFisher) at both institutions (CEMIC/HIBA). Patients with KRAS mutational status assessed by PCR/sanger sequencing at CEMIC were also included. We estimated the prevalence and type of KRAS mutations using both testing methods. We estimated the overall survival (OS) of patients from the date of metastatic disease diagnosis using Kaplan-Meier. The prevalence of KRAS mutations using NGS was 23% (35/150) and was 19% (16/84) using PCR/sanger sequencing. The prevalence of KRAS G12C was 10,6% (16/150) with NGS and 6% (5/84) using sanger sequencing. KRAS G12C accounted for 41% of KRAS mutations in the entire cohort of, followed by G12V (24%), G12D (8%), G13C (6%) and G12A (6%), G12S (4%), G13D (4%), G13S (4%), Q61H (2%) and one commutation (2%). In the 51 patients with KRASm NSCLC included, the median age (IQR) was 66 years (61-72.5), there was a higher proportion of male patients (65%) and smoking history (94%), and the most tumor histology was adenocarcinomas (94%). In total, 39 patients had metastatic disease of which 90% received treatment. First line treatment included chemotherapy (n=33, 94%), immunotherapy (n=2, 6%). 20 patients (51%) received second line treatment with immunotherapy (n=15) and chemotherapy (n=5). With a follow up median of 38 months (IC 95%: 21.6-47.9), the median overall survival of patients with metastatic disease was 14.2 months (IC 95%: 7.7-30.3). KRAS mutations occur in about 23% of patients with NSCLC and KRAS G12C mutations in 10.6% of patients using NGS. This is similar to previously reported data in other western countries, and higher than reported in overall in Latin America. Extensive molecular profiling of lung cancer can identify potentially targetable KRAS G12C mutations and help to select a subgroup of patients that can benefit with clinical trials targeting KRAS.