The genomics of young lung cancer.

9083 Background: Lung cancer is increasingly understood as a disease made up of genomically defined subtypes requiring distinct treatment strategies. We hypothesize that young age at diagnosis ( < 40 years) is a clinical characteristic associated with an increased chance for a targetable genomic alteration (GA). Our study will prospectively characterize the somatic and germline genomics of young lung cancer. Methods: Accrual opened in July 2014. Patients (pts) are eligible if diagnosed with bronchogenic lung cancer < age 40. The study website, https://www.openmednet.org/site/alcmi-goyl allows for virtual consenting and remote participation from anywhere in the world. We defined 7 GA of interest based on the Lung Cancer Mutation Consortium (LCMC) (EGFR, KRAS, HER2, BRAF, ALK, ROS1, RET). We aim to show the prevalence of targetable GA in our stage 4 adenocarcinoma (AC) pts will be greater in our population compared to the LCMC, with an increase from 35% to 50%; and an improvement in use of targeted therapy from 22% to 40%. Study subjects without a known genotype undergo genomic profiling with the FoundationOne test. Results: Preliminary results of 63 pts with stage 4 AC show that 83% have either an ALK re-arrangement n = 29 (46%), an EGFR activating mutation n = 16 (25%), a ROS1 fusion n = 4 (6%), a RET fusion n = 2 (3%) or a HER2 mutation n = 2 (3%). Other GA of interest in 22% with AC includes TP53, ATM and BRCA2 mutations. Though numbers are small, analysis of exposures show findings including: ROS1 fusion pts are never smokers, without exposure to secondhand smoke and compared to those with EGFR and ALK mutations, had a higher proportion of family history of lung cancer (60% vs. 25%). Conclusions: The trial is currently accruing (NCT02273336). Thus far in our prospective series our results have far exceeded our statistical expectations, with 83% of our stage 4 AC pts having an actionable mutation. We have defined a genomically enriched subtype of lung cancer and laid the groundwork for further studies of germline and environmental lung cancer risk factors and thus, are planning a large-scale Case Control study of the Epidemiology of YLC. (Final study results of 2 years of accrual will be presented at ASCO 2016 meeting). Clinical trial information: NCT02273336.