Comparative Clinical Outcomes for Patients With Advanced NSCLC Harboring EGFR Exon 20 Insertion Mutations and Common EGFR Mutations

Abstract Introduction Real-world clinical outcomes in patients with advanced NSCLC harboring EGFR exon 20 insertion (exon20ins) mutations have not been extensively studied. We conducted a retrospective cohort study to assess the clinical outcomes of EGFR exon20ins compared with common EGFR (cEGFR) mutations. Methods Adults with advanced NSCLC harboring any EGFR mutations in the NSCLC Flatiron registry (2011 through May 2020) were included. To compare the relative prognosis (prognostic value) of exon20ins vs cEGFR, real-world overall survival (rwOS) was the primary endpoint. Separately, to compare the relative response to tyrosine kinase inhibitor (TKI) treatment (predictive value), real-world progression-free survival (rwPFS) was the primary endpoint. Results For the prognostic value analysis, 3014 patients with EGFR mutant NSCLC (cEGFR, n=2833; EGFR exon20ins, n=181) were eligible. The median (95% CI) rwOS was 16.2 (11.04-19.38) months in the EGFR exon20ins cohort vs 25.5 (24.48-27.04) months in the cEGFR cohort (adjusted HR, 1.75 [1.45-2.13]; p  Conclusions Patients with EGFR exon20ins have poor prognosis and receive little benefit from EGFR TKI treatment. More effective therapies are needed in this difficult-to-treat population.