Real-World Analysis of Post-Progression Treatment Patterns and Outcomes for EGFR Mutation-Positive Patients Treated with First-Line Osimertinib.

Introduction: The use of osimertinib in the first-line (1L) setting is an effective treatment option for sensitizing EGFR-mutations (EGFRm+) and has significantly altered the standard of care practice for EGFRm+ disease in Canada. Unfortunately, acquired resistance to osimertinib is almost universal, and outcomes are disparate. Post-progression treatment patterns and the outcome of real-world Canadian EGFRm+ patients receiving 1L osimertinib were the focus of this retrospective review. Methods: The Glans-Look Lung Cancer Research database was used to identify and collect demographic, clinical, treatment, and outcome data on EGFRm+ patients who received 1L osimertinib in the Canadian province of Alberta between 2018 and 2022. Results: A total of 150 patients receiving 1L osimertinib were identified. In total, 86 developed progressive disease, with 56 (65%) continuing systemic therapy, 73% continuing osimertinib, and 27% switching to second-line (2L) systemic therapy. Patients were similar both in clinical characteristics at 1L osimertinib initiation and patterns of treatment failure at progression; those continuing 1L osimertinib post-progression had a longer time to progression (13.5 vs. 8.8 months, p = 0.05) and subsequent post-osimertinib initiation survival (34.7 vs. 22.8 months, p = 0.11). Conclusions: The continuation of osimertinib post-progression is an effective disease management strategy for select real-world EGFRm+ patients, providing continued clinical benefit, potentially due to different underlying disease pathogenesis.

Impact of number versus location of metastases on survival in stage IV M1b non-small cell lung cancer.

BACKGROUND: To assess the impact of location versus number of extra-pulmonary metastatic sites (EPMS) on survival in stage IV non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Retrospective analysis was conducted on patients diagnosed during 1999-2013 with stage IV, M1b (AJCC 7th edition) NSCLC using the large, institutional Glans-Look Database, which contains patient demographic, clinical, pathological, treatment, and outcome information. We assessed the impact of location and number of EPMS and identified correlates of overall survival using the Kaplan-Meier method and Cox regression. RESULTS: We identified a total of 2065 NSCLC patients with EPMS. Median age was 67 (IQR 58-75) years, 52% were men, and 78% were current or former smokers. 60% had one EPMS, and 40% had two or more EPMS. Among those with only one EPMS, most frequent organ involvement included bone (40%), brain (32%), and liver (13%). Median overall survival (mOS) was worst in those with liver metastasis and best in those with adrenal metastasis (2.0 vs. 5.2 months, p = 0.015). However, outcomes based on site of organ involvement were not significantly different in multivariable analysis. Compared to patients with one EPMS, individuals with two or more EPMS experienced worse outcomes (mOS ≤ 2.9 vs. 3.9 months, p < 0.001), and were associated with worse prognosis in Cox regression analysis (HR 1.5, 95% CI 1.3-1.7, p < 0.001). CONCLUSIONS: Number rather than location of EPMS is a prognostic factor in patients with stage IV M1b NSCLC. This information is relevant for accurate prognostication, stratification of participants in future clinical trials, and timely and appropriate advanced care planning.