Concurrent genetic alterations identified by next-generation sequencing in pre-treatment, metastatic EGFR-mutant lung cancers.

作者：Helena Alexandra Yu, Emmet Jordan, Ai Ni, Daniel Feldman, Christopher Rodríguez, Hyunjae Ryan Kim, Mark G. Kris, David B. Solit, Michael F. Berger, Marc Ladanyi, Maria E. Arcila, Gregory J. Riely · 发表于：Journal of Clinical Oncology · 年份：2016 · DOI：10.1200/jco.2016.34.15_suppl.9053 · 被引用次数：13 · 研究领域：Lung Cancer Treatments and Mutations、Cancer Genomics and Diagnostics、Radiomics and Machine Learning in Medical Imaging

9053 Background: Whether disease characteristics or outcomes for patients (pts) with EGFR-mutant lung cancers differ by co-mutations present is unknown. In order to understand the impact of co-mutations, we reviewed molecular results, disease course and clinical characteristics of pts with untreated, metastatic EGFR-mutant lung cancers. Methods: We identified all pts with untreated EGFR-mutant metastatic lung cancers who had targeted NGS performed from Jan 2014 to Sept 2015. Molecular alterations in 341 genes were assessed. Fisher’s exact and log rank tests were used to identify associations between co-mutations and presence of central nervous system metastases, progression-free survival (PFS) on EGFR tyrosine kinase inhibitor (TKI) and overall survival (OS). Results: Activating kinase-domain mutations in EGFR were identified in 95 pts (exon 19 deletion = 43, L858R = 33, exon 20 insertion = 10, other = 9). The median depth of coverage was 654x; the median number of co-mutations was 5 (range 0-28). 242 unique co-mutations were identified. Median age: 63, women: 69%, never smokers: 58%, adenocarcinoma: 96%. The most frequent co-mutations were TP53 (62%), PIK3CA (14%), and RB1 (11%). The most frequent amplifications were seen in EGFR (26%) and NKX2.1/TTF-1 (13%). 1 sample had concurrent subclonal KRAS Q61H and EGFR L858R mutations. There were no concurrent ALK/ROS1/RET rearrangements. Co-mutations did not differ by EGFR mutation subtype. There was no association between co-mutat...