Landscape of Genomic Alterations (ga) Detected by Next-Generation Sequencing (ngs) in Non-Small Cell Lung Cancer (nsclc) Adenocarcinoma in Israel.

e19111 Background: Profiling lung cancer tumors for targetable GAs is the cornerstone for individualizing treatment for this disease. We hypothesized that NSCLC samples would be enriched in actionable GAs in targetable genes. Methods: The analysis included all Israeli patients (pts) with NSCLC adenocarcinoma who underwent comprehensive NGS testing (FoundationOne) between 10/2011 and 12/2013. NGS was performed on hybridization-captured adapter-ligated libraries using DNA extracted from NSCLC specimens. It covered 3,769 exons from 236 cancer-related genes and 47 introns from 19 genes commonly rearranged in cancer. GAs including base substitutions, small indels, copy number alterations, and select gene fusions were characterized for each pt sample. Actionable GAs were defined as those identifying anti-cancer targeted therapies (commercially available or in registered clinical trials). NGS was performed as a commercially available service; the analysis was approved by the IRBs of all participating centers. Results: The analysis included 58 pts. Median (range) age was 60 (20-82) yrs and 33 (57%) were lifelong non-smokers. At the time of NGS testing, ≥74% of pts were pre-tested for EGFR and ALK, and 3 and 1 pts were positive, respectively. Samples used for NGS originated from the primary tumor in 34 pts (59%) and from metastatic lesions in 24 pts (41%). All 58 samples harbored ≥ 1 GA (mean: 3.2 GAs/tumor). The most frequent currently non-actionable GAs were identified in TP53 (53%) and RB1 (14 %). Fifty four pts (93%) harbored ≥ 1 actionable GA (mean: 1.7 actionable GAs/tumor). The most common actionable GAs were KRAS (29 %), EGFR (26 %), and CDKN2A (14 %). Gene fusions included ALK and RET both at 7%, and a rare TACC3-FGFR3 fusion (2%). Notably, NGS identified GAs in EGFR and ALK in pts whose prior EGFR/ALK testing was negative (6/43 [14%] and 2/42 [5%], respectively). GAs in the ERBB2 gene were observed in 4 samples (7%); all had insertion mutations with no amplifications. Conclusions: NGS of NSCLC samples revealed a high rate of actionable GAs in well-known anti-cancer targets, which were all mutually exclusive. Further analysis of this enhanced targetable GA rate appears warranted.