Second-line therapy following osimertinib in metastatic EGFR-mutated non-small cell lung cancer at an academic medical center

Purpose: 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 lline osimertinib, raising the concern that FLAURA2 did not accurately reflect real world practices at academic medical centers. We hypothesized that a higher proportion of patients on osimertinib monotherapy receive second-line therapy at academic medical centers in the United States (US). Patients and Methods: 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 US from February 2018 to July 2024. Analyses included Kaplan-Meier survival estimation, the log-rank test, multivariate Cox regression, and the Kruskal-Wallis test. Results: Most patients were female (74%) and had a history of never-smoking (69%). Fifty percent 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 16.3 months (CI: 13.3-22.0) for TP53-mutated patients and 42.3 months (CI: 36.9-NA) for TP53 wild-type patients (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. Conclusions: Only 61% of patients with metastatic EGFR-mut NSCLC received second-line therapy after osimertinib at our institution, confirming that the second-line therapy rates in the control arm of FLAURA2 are similar to practice patterns at our US academic medical center.