Second-Line Therapy Following Osimertinib in Metastatic EGFR-Mutated Non-Small-Cell Lung Cancer at an Academic Medical Center.

BACKGROUND: FLAURA2 demonstrated that adding chemotherapy to osimertinib improved overall survival compared with osimertinib monotherapy in metastatic epidermal growth factor receptor-mutated (EGFR-mut) non-small-cell lung cancer (NSCLC). Notably, only 60% of patients in the osimertinib monotherapy arm received second-line therapy after discontinuing first-line osimertinib. Aims We hypothesized that a higher proportion of patients on osimertinib monotherapy receive second-line therapy at academic medical centers in the United States (US). METHODS AND RESULTS: This is a retrospective cohort study of 115 patients with metastatic EGFR-mut NSCLC treated with first-line osimertinib monotherapy at an academic medical center in the United States from February 2018 to July 2024. Analyses included Kaplan-Meier survival estimation, log-rank test, multivariate Cox regression, Wilcoxon rank-sum test, and Fisher's exact test. Most patients were female (74%) and had a history of never-smoking (69%); 50% were Asian, and 93% of patients had adenocarcinoma histology. The median time to treatment failure (TTF) for all patients on first-line osimertinib was 25.3 months (95% CI: 18.6-37.5). The median TTF was 15.7 months (CI: 13.1-22.0) for patients with TP53-mut disease and 42.2 months (CI: 36.9-NR) for patients with TP53 wild-type tumors (log-rank test, p < 0.001). Of the 115 total patients, 66 (57.4%) discontinued first-line osimertinib. Of these 66 patients, 26 (39.4%) either died or pursued hospice. Forty (60.6%) of the 66 patients experienced progression of disease and subsequently received second-line therapy. CONCLUSION: Only 61% of patients with metastatic EGFR-mut NSCLC received second-line therapy after osimertinib at our institution, similar to the second-line therapy rates in the control arm of FLAURA2.