Impact of EGFR amplification on survival of patients with EGFR exon 20 insertion-positive non-small cell lung cancer

Background: Epidermal growth factor receptor (EGFR) exon 20 insertion (EGFR ex20ins) is a common mutation in non-small cell lung cancer (NSCLC). Patients with EGFR ex20ins generally respond poor to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). EGFR ex20ins are often co-occurring with EGFR amplification. However, the impact of EGFR amplification on the survival of patients with EGFR ex20ins mutations has not been determined. Methods: This is an observational longitudinal cohort study. A prospectively managed database included consecutive treatment-naive adult patients with advanced NSCLC and EGFR ex20ins confirmed by next-generation sequencing (NGS) at Guangdong Provincial Peoples Hospital between November 2017 and February 2019. The participants were enrolled from the database and extracted their clinical characteristics, treatment and clinical outcomes. NGS was used to establish whether EGFR amplification was present in tumor tissue. Overall survival (OS) and progression-free survival (PFS) were compared between EGFR amplification and non-EGFR amplification groups using the Kaplan-Meier method and log-rank test. Subgroup analyses were performed based on the treatment used (EGFR-TKI or chemotherapy). Results: Fifteen different EGFR ex20ins mutation subtypes were identified in the 39 patients included in the analysis, and the most common subtypes were p.A767_D770dup (25.6%), p.S768_D770dup (23.1%) and p.N771_H773dup (10.3%). Among 31 patients with EGFR ex20ins mutations and NGS data for tumor tissue, EGFR amplification was identified in 12 patients (38.7%) and there were no significant differences in clinical characteristics. Among 26 patients, there were no significant differences between the EGFR amplification (n=11) and non-EGFR amplification (n=15) groups in median OS (715 vs. 452 days, P=0.912). Among 20 patients administered chemotherapy, there were no significant differences between the EGFR amplification and non-EGFR amplification groups in median PFS (206 vs. 112 days, P=0.425). Among 24 patients administered an EGFR-TKI, median PFS was longer in the non-EGFR amplification group than in the EGFR amplification group (110 vs. 31 days, P=0.030). Conclusions: There is a tendency that EGFR amplification might be a poor predictor in EGFR ex20ins-positive NSCLC patients treated with EGFR-TKIs.