Comparative clinical outcomes for patients with advanced NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations

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 [1.45-2.131; p < 0.0001); 5-year rwOS was 8% and 19%, respectively. For the predictive value analysis, 2825 patients received TKI treatment and were eligible (cEGFR, n = 2749; EGFR exon20ins, n = 76). The median (95% CI) rwPFS from start of the first TKI was 2.9 (2.14-3.91) months in the EGFR exon20ins cohort vs 10.5 (10.05-10.94) months in the cEGFR cohort (adjusted HR, 2.69 [2.05-3.541; p < 0001). Among patients with EGFR exon20ins, the most common prescribed first-line therapy was platinum-based chemotherapy (61.3%) followed by EGFR TKIs (21.5%); second-line treatments were varied, with no clear standard of care. 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.