LAUSR

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), n1⁄428 were men (55%), smoker/former-smoker/non-smoker n1⁄411 (21.6%)/ n1⁄431 (60.8%)/ n1⁄49 (17.6%), Stage IIIa n1⁄47 (13.7%), IIIb n1⁄46 (11.8%), IV n1⁄438 (74.5%). Adenocarcinoma histology n1⁄443 (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 n1⁄418 (35%), EGFR n1⁄48 (17.6%) BRAF n1⁄42 (4%), METex14 skipping n1⁄42 (4%), HER2 n1⁄41 (2%), ALK rearrangements n1⁄45 (10%) y ROS1 rearrangements n1⁄42 (4%). Co-mutations: EGFR+BRAF n1⁄41, ALK+KRAS n1⁄41, KRAS+AKT n1⁄41. 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.