In silico analysis of DNA damage repair variants in advanced NSCLC patients (pts) to predict response to platinum-based chemotherapy (PBC).

e20582Background: There are no biomarkers that reliably predict benefit from PBC in NSCLC. We hypothesize cancers with DNA damage repair pathway nsSNPs may be more sensitive to PBC. Methods: Pts with advanced NSCLC that received first-line PBC and next-generation sequencing (NGS) with Caris (2013-2015) were retrospectively identified. The total pathogenic burden (SUM) was defined as test-determined pathogenic mutations (Pmut) plus nsSNPs predicted-damaging (pnsSNPs) by in silico analysis with PolyPhen-2 (Harvard). 13 DNA damage repair genes were also selectively analyzed. All p-values were two-tailed. Results: 84 pts were found; 35% female; 58% white, 37% black; median age was 64 (range 26-81); 82% had ≥20 pack-years (py), 12% with < 20 and 6% never-smokers; 27% received immunotherapy (IT) and 5% tyrosine kinase inhibitors (TKI) subsequently. 49 pts had primary progressive disease (58%), 9 stable disease (11%), 16 partial response (19%) and 10 complete response (12%). Median overall survival (OS) was 11 m...