Overall Survival in EGFR-Mutant Advanced NSCLC Treated With First-Line Osimertinib: A Cohort Study Integrating Clinical and Biomarker Data in the United States

Joshua K Sabari; Helena A Yu; Parthiv J Mahadevia; Yanfang Liu; Levon Demirdjian; Yen Hua Chen; Xiayi Wang; Antonio Passaro

doi:10.1016/j.jtho.2025.04.010

Overall Survival in EGFR-Mutant Advanced NSCLC Treated With First-Line Osimertinib: A Cohort Study Integrating Clinical and Biomarker Data in the United States

J Thorac Oncol. 2025 May 2:S1556-0864(25)00699-9. doi: 10.1016/j.jtho.2025.04.010. Online ahead of print.

Authors

Joshua K Sabari¹, Helena A Yu², Parthiv J Mahadevia³, Yanfang Liu³, Levon Demirdjian⁴, Yen Hua Chen³, Xiayi Wang⁵, Antonio Passaro⁶

Affiliations

¹ Perlmutter Cancer Center, New York University Langone Health, New York, New York.
² Memorial Sloan Kettering Cancer Center, New York, New York.
³ Johnson & Johnson, Raritan, New Jersey.
⁴ Johnson & Johnson, San Diego, California.
⁵ Johnson & Johnson, Titusville, New Jersey.
⁶ European Institute of Oncology IRCCS, Milano, Italy. Electronic address: Antonio.Passaro@ieo.it.

PMID: 40320171
DOI: 10.1016/j.jtho.2025.04.010

Abstract

Introduction: Patients with NSCLC harboring EGFR mutations (EGFRm) have high mortality. The third-generation tyrosine kinase inhibitor, osimertinib, is approved for first-line EGFRm NSCLC. We used longitudinal U.S. medical oncology databases to evaluate real-world overall survival (rwOS) and 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 or 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: A total of 1323 patients were included with a median follow-up of 20 months. Median age was 70 (range 35-89) years. Median rwOS was 28.6 months (95% confidence interval 26.8-30.9). In high-risk subgroups, median rwOS (mo) was 18.1 in patients with Eastern Cooperative Oncology Group score greater than or equal to 2, 24.3 with brain metastases, 19.3 with liver metastases, and 25.7 with TP53 co-mutation. In total, 95% of patients had at least one high-risk factor. Prevalence of Eastern Cooperative Oncology Group greater than or equal to 2 was 17%, brain metastases 36%, liver metastases 15%, and 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 tyrosine kinase inhibitor 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.

Keywords: Epidermal growth factor receptor; Non–small cell lung cancer; Osimertinib; Risk factors; Survival.