Real-World Clinical Outcomes and Treatment Patterns in Advanced/Metastatic EGFR-Mutant NSCLC After Progression on First-Line Osimertinib for French Patients.

[INTRODUCTION] Osimertinib, a third-generation tyrosine kinase inhibitor (TKI), is a standard first-line (1L) treatment for advanced/metastatic EGFR non-small cell lung cancer (NSCLC). Despite improved overall survival (OS) and progression-free survival (PFS) compared to earlier generation TKIs, resistance and disease progression are common. No standardized second-line (2L) treatment exists for patients who progress after 1L osimertinib. This study assessed real-world (rw) treatment patterns and clinical outcomes in French patients with advanced/metastatic NSCLC who received 2L therapy post-osimertinib progression.

[METHODS] This retrospective, observational study used the Epidemio-Strategy and Medical Economics (ESME) LC database (NCT03848052) (January 1, 2015-2023; data extraction September 2023). Patients ≥ 18 years with confirmed advanced/metastatic NSCLC, treated with 1L osimertinib, and documented 2L therapy were included. The study assessed patient characteristics, rw treatment patterns, rwOS, and rwPFS.

[RESULTS] Among 284 patients (71.1% female, median age 67), 67% initiated 2L treatment in 2021 or later. The median number of metastases at 2L initiation was three, with bone (65.1%) and brain (56.6%) as the most common sites; 34% of brain metastases were symptomatic. The 2L treatments included platinum-based chemotherapy (50%), EGFR TKI-based therapy (29.9%), immunotherapy (9.9%), and other regimens (10.2%). Median rwOS from 2L initiation was 10.1 (95% CI 9.2-12.1) months, and median rwPFS was 4.1 (95% CI 3.3-4.8) months. Among patients with brain metastases, median rwOS was 8.7 (95% CI 7.1-11.9) months for asymptomatic and 10.7 (95% CI 9.4-12.9) months for symptomatic patients vs 11.8 (95% CI 9.1-17.4) months in patients without brain metastases. Patients with liver metastases had a median rwOS of 8.2 (95% CI 6.4-9.6) months vs 12.3 (95% CI 10.2-14.3) months in those without.

[CONCLUSIONS] Clinical outcomes for patients receiving 2L therapy post-osimertinib progression remain poor, highlighting an unmet need, particularly for those with brain and liver metastases.