P22 ASTRIS a RWT with Osimertinib in NSCLC EGFR T790M Mutated: Disease Characteristics from Patients Included in Argentina

Abstract

Background: Profiling of targetable oncogenic drivers has significantly improved outcomes in patients with nonesmall cell lung cancer (NSCLC). About 40% of individuals with metastatic lung adenocarcinomas may benefit from personalized treatment with kinase inhibitors. There is limited data of the distribution of oncogenic drivers other than ALK and EGFR in our region. In this study we performed next generation sequence (NGS) to study the distribution of molecular alterations in patients with advanced lung cancer. Herein we present preliminary data of a single center experience. Method: A prospective, single-center, observational study was conducted. We included 125 patients > 18 years old with NSCLC from 06/2015 to 06/2018. NGS was performed with DNA/RNA from formalin-fixed, paraffin-embedded (FFPE) tumor tissue with OncomineTM Focus Assay (Ion 520 Chip), sequenced in Ion S5 Next Generation Sequencing Systems, analyzed with Ion ReporterTM Software 5.2.1 and informed with Ion TorrentTM OncomineTM Knowledgebase Reporter. Results were compared with those from standard pathology and molecular biology techniques, when available, like immunohistochemistry (IHQ) and FISH for ROS1 and ALK and PCR and sequencing for EGFR. We report partial results from the first 51 patients included. Results: Median (IQR) age was 65 years (59-74), n¼28 were men (55%), smoker/former-smoker/non-smoker n¼11 (21.6%)/ n¼31 (60.8%)/ n¼9 (17.6%), Stage IIIa n¼7 (13.7%), IIIb n¼6 (11.8%), IV n¼38 (74.5%). Adenocarcinoma histology n¼43 (84.3%). Assay performance was 100% for DNA analysis and 60.8% for the study of fusions and CNV from RNA. Distribution of molecular alterations: KRAS n¼18 (35%), EGFR n¼8 (17.6%) BRAF n¼2 (4%), METex14 skipping n¼2 (4%), HER2 n¼1 (2%), ALK rearrangements n¼5 (10%) y ROS1 rearrangements n¼2 (4%). Co-mutations: EGFR+BRAF n¼1, ALK+KRAS n¼1, KRAS+AKT n¼1. Conclusion: NGS allows to optimize the molecular profiling of tumors from patients with lung cancer in our population. It can simultaneously identify mutations, rearrangements and alternative splicing events in key oncogenic drivers that can select patients to treatment with kinase inhibitors, currently available in the daily practice and in clinical development.