LAUSR

Introduction: EGFR‐mutant NSCLC displays diverse outcomes to tyrosine kinase inhibitor (TKI) treatment. Because co‐occurring genomic alterations might describe different biological subsets of patients with this cancer, exploring co‐occurring genomic alterations that impact patients’ outcomes using a comprehensive gene panel is potentially important. Methods: This retrospective cohort study was conducted with the panel‐sequencing data acquired from January 2014 to May 2017, and clinical outcome data collected until February 2018. This study includes all eligible patients who possess panel‐sequencing data before treatment with first‐/second‐generation EGFR‐TKIs (cohort 1) or third‐generation EGFR‐TKIs following initial EGFR‐TKI failure (cohort 2). Results: Seventy‐five patients (mean [SD] age, 58.5 [11.0] years; 68.0% women) were included in cohort 1, and 82 patients (mean [SD] age, 57.3 [9.1] years; 67.1% women) were included in cohort 2. In cohort 1, alterations in TP53 were independently associated with worse progression‐free survival (PFS) (hazard ratio [HR]: 2.02; 95% confidence interval [CI]: 1.04–3.93; p = 0.038) in multivariate analysis. In cohort 2, TP53 mutation was associated with significantly worse PFS (8.9 versus 12.8 months; p = 0.029). RB1 mutation was significantly associated with worse (median PFS, 1.9 versus 11.7 months; p < 0.001). PTEN mutation was associated with significantly worse PFS (2.6 versus 10.3 months; p = 0.001). MDM2 amplification was associated with worse PFS (6.6 versus 10.4 months; p = 0.025). In cohort 2, multivariate analysis revealed that alterations in TP53 (HR: 2.23; 95% CI: 1.16–4.29; p = 0.017), RB1 (HR: 5.62; 95% CI: 1.96–16.13; p = 0.001), PTEN (HR: 5.84; 95% CI: 1.56–21.85; p = 0.009), and MDM2 (HR: 2.46; 95% CI: 1.02–5.94; p = 0.046) were independently associated with worse PFS. Conclusions: Co‐occurring genomic alterations detected by panel sequencing are associated with the clinical outcomes of EGFR‐TKI treatment in NSCLC.