Overall Survival in EGFR-mutant Advanced Non-Small Cell Lung Cancer Treated with First-line Osimertinib: A Cohort Study Integrating Clinical and Biomarker Data in the United States.

Introduction: Patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations (EGFRm) have high mortality. The third-generation tyrosine kinase inhibitor (TKI) osimertinib is approved for first-line EGFRm-NSCLC. We used longitudinal US medical oncology databases to evaluate real-world overall survival (rwOS) prognostic risk factor groups in advanced EGFRm-NSCLC treated with first-line osimertinib.

Methods: This retrospective, new-user cohort study used electronic records from ConcertAI, Flatiron Clinical-Genomics, and COTA databases. Patients with advanced/metastatic EGFRm-NSCLC initiating osimertinib monotherapy in first-line between April 1, 2018 and October 30, 2022 were included. Follow-up was until death or October 31, 2023. rwOS was estimated using the Kaplan-Meier method. Risk factors were evaluated using multivariate analysis.

Results: 1323 patients were included with median follow-up of 20 months. Median age was 70 years (range 35-89). Median rwOS was 28.6 months (95% CI 26.8-30.9). In high-risk subgroups, median rwOS (months) was 18.1 in patients with ECOG score ≥2, 24.3 with brain metastases, 19.3 with liver metastases, and 25.7 with TP53 co-mutation. 95% of patients had ≥1 high risk factor. Prevalence of ECOG ≥2 was 17%, brain metastases 36%, liver metastases 15%, TP53 co-mutation 63%. Risk of death was significantly higher in patients with high-risk factors (p≤0.011 for all). In total, 58% of patients survived to 2 years, 18% to 5 years, and 33% did not receive second-line therapy.

Conclusion: Despite advances in TKI treatments, long-term survival of patients with advanced EGFRm-NSCLC remains poor. Nearly all patients had risk factors for mortality and one-third did not receive second-line therapy.