Abstract
INTRODUCTION: Osimertinib is recommended, alongside afatinib, as first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) with atypical mutations in the epidermal growth factor receptor gene (EGFR), a population for whom real-world data are limited. We present outcomes and subsequent treatment patterns for this population in routine US practice. METHODS: Medical records from a manually curated oncology database were analyzed for adults with stage IIIB-IV NSCLC harboring atypical EGFR mutations, treated with first-line osimertinib (April 2018-March 2020). Data were analyzed overall and by EGFR mutation subgroups: compound EGFR mutations, comprising classical (exon [Ex] 19 deletion or L858R) and atypical (G719X, L861Q, S768I, E709X, Ex19 insertions, or Ex18-25 duplications) mutations or de novo T790M only (group A), and atypical EGFR mutations only (group B). Outcomes included real-world progression-free survival (rwPFS) and overall survival (OS). RESULTS: A total of 55 patients were included in the study (female 76%/male 24%; group A, n = 20; group B, n = 35). After a median follow-up of 11 months, median (95% confidence interval) rwPFS and OS, respectively, were 8.8 (5.5-17.2) and 28.5 months (11.4-41.8) overall, 20.3 (10.0-44.5) and 42.5 months (27.0-not estimable) in group A, and 6.6 (4.9-24.8) and 20.0 months (9.2-32.9) in group B. At follow-up, 13% of patients (n = 7) remained on first-line osimertinib (group A, 30%; group B, 3%), 54% (n = 30) had discontinued due to death (group A, 40%; group B, 63%), and 33% (n = 18) had received subsequent treatment (group A, 30%; group B, 34%), most commonly osimertinib combinations (28%; n = 5). CONCLUSIONS: First-line osimertinib may provide real-world clinical benefits for patients with advanced NSCLC with atypical EGFR mutations, with results suggesting greater benefit in those harboring compound EGFR mutations.