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

e20653 Background: FLAURA2 demonstrated that adding chemotherapy to osimertinib improved progression-free survival compared to osimertinib monotherapy in metastatic Epidermal Growth Factor Receptor mutated (EGFR-mut) non-small cell lung cancer (NSCLC). Although overall survival data is immature, there is a trend that favors osimertinib and chemotherapy. Notably, only 60% of patients in the osimertinib monotherapy arm received second-line therapy after discontinuing first-line 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). Methods: This is a retrospective cohort study of 115 patients with metastatic classical EGFR-mut NSCLC treated with first-line osimertinib monotherapy at an academic medical center in the US from February 2018 to July 2024. Data were abstracted from medical records, descriptive statistics were calculated, and Kaplan-Meier survival analysis and the Kruskal-Wallis test were performed. Results: Median age at diagnosis was 69 years old. Most patients were female (73.9%), had history of never-smoking (68.7%), and had adenocarcinoma histology (93.0%). Forty-nine point six percent were Asian. Median time to treatment failure (TTF) with minimum follow-up time of 24 months for all patients on first-line osimertinib was 19.3 months (95% CI: 16.2–31.4). Median TTF was 14.2 months (CI: 12.6–17.6) for TP53-mutated patients and 42.2 months (CI: 34.4–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%) died or pursued hospice. Forty (60.6%) of the 66 patients experienced progression and received second-line therapy. The most common second-line therapies were chemotherapy (75%), immune checkpoint inhibitors (17.5%), and VEGF-inhibitors (7.5%). Patients who did not receive second-line therapy had a median age (IQR) of 77.7 (70.5–82.2), compared with 64.9 (60.3–71.3) for those who did receive second-line therapy and 69.2 (61.5–78.4) for patients continuing first-line osimertinib (Kruskal-Wallis test: p < 0.001). Conclusions: Only 61% of patients with metastatic EGFR-mut NSCLC received second-line therapy after osimertinib at our academic medical center. Our results show that second-line therapy rates in the control arm of FLAURA2 are similar to practice patterns at our US academic medical center. Outcomes Number of Patients Percentage Median Age IQR Total Patients 115 - - - Continuing first-line osimertinib 49 42.6% 69.2 [61.5–78.4] Discontinued first-line osimertinib 66 57.4% - - Received second-line therapy 40 60.6% 64.9 [60.3–71.3] Did not receive second-line therapy 26 39.4% 77.7 [70.5–82.2]