Abstract B45: Upfront genomic testing in non-small cell lung cancer (NSCLC) patients: Preliminary result of the MSN study

Background: Recent advances in lung cancer have identified potential driver mutations that may be targeted. To identify new predictors of response as well as novel targets for therapy, we have initiated a comprehensive large-scale sequencing analysis of genes potentially mutated in NSCLC. Methods: Genomic DNA was extracted prospectively from untreated advanced NSCLCs. All tumors were obtained on IRB-approved protocols and after patients9 consent (MSN trial “Melanoma – Small-cell lung cancer – Non-small cell lung cancer”). Pathology specimens were macrodissected in order to obtain more than 30% of tumor cells and, after DNA extraction, 96 selected exons from 30 genes were analyzed by Sanger sequencing. ALK rearrangements were detected by fluorescence in-situ hybridization. All results were discussed monthly in a molecular thoracic multidisciplinary staff. Second or third lines of treatment were adapted to mutation profiling. Results: Thus far (between 09/01/2010 and 06/01/2011), 82 tumors have been analyzed for AKT, ALK, APC, BRAF, CTNNB1, EGFR, ERBB2, FBXW7, FGFR2-3, GNAQ, GNAS, HRAS, KIT, KRAS, MAP2K1-2, MET, NOTCH1, NRAS, PDGFRA, PI3KCA, PTEN, RET, STK11, TP53, and VHL mutations. The median age was 60 years (range 26–76), 29 (35%) were female, 58 (70%) had adenocarcinoma, 72 (67%) were former/current smokers. Nine patients had incomplete genomic analysis due mostly to insufficient tumor cells in the specimen or poor quality DNA. Median tumor cells ratio was 50%. Mutations were identified in 43/82 (52%) patients (EGFR: 9; KRAS: 10; STK 11: 8; BRAF: 4; MET: 2; PTEN: 2; NRAS: 1; ERBB2: 1; PIK3CA: 1…) of whom 11 had concurrent mutations. EGFR and KRAS mutations were mutually exclusive. No mutations were identified among 5 never smokers analyzed. The median time to complete testing for this initial phase was 30 days. Half of patients with genomic alterations were treated with molecularly targeted therapy based on their genetic alteration. Conclusions: Mutational profiling of NSCLC is feasible, can distinguish relevant molecular subsets of lung cancer, and may present an impact on treatment at our cancer institute. Furthers sequencing are in progress and updated results will be presented in January 2012.