Mutation testing, treatment patterns, and outcomes in patients with unresectable stage III EGFR-mutated non-small cell lung cancer treated with chemoradiotherapy: Final analysis of a global real-world study
- PMID: 41151357
- DOI: 10.1016/j.lungcan.2025.108748
Mutation testing, treatment patterns, and outcomes in patients with unresectable stage III EGFR-mutated non-small cell lung cancer treated with chemoradiotherapy: Final analysis of a global real-world study
Abstract
Introduction: In the phase III LAURA study, osimertinib after definitive chemoradiotherapy (CRT) demonstrated a statistically significant, clinically meaningful progression-free survival (PFS) benefit over placebo in patients with unresectable stage III epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Understanding real-world (rw) treatment patterns and clinical outcomes can help to measure the impact of new treatments. We report final results from a global, retrospective rw study of patients with unresectable stage III EGFR-mutated NSCLC treated with CRT.
Materials and methods: Data were extracted from medical records of adults with unresectable stage III EGFR-mutated (Ex19del/L858R) NSCLC, diagnosed January 2016-December 2019, who received CRT as standard of care. The primary outcome was rwPFS. Secondary outcomes included mutation testing patterns and treatment patterns, rw time to next treatment or death (rwTTNTD) and overall survival (OS). Analyses are descriptive; time-to-event outcomes were estimated using Kaplan-Meier methods.
Results: Data were included from 172 patients; 59 % of patients harbored Ex19del and 41 % L858R; 76 % received concurrent CRT and 24 % sequential CRT. Overall, 78 %, 18 %, 3 %, and 1 % of patients received CRT alone, CRT plus durvalumab, CRT plus an EGFR-tyrosine kinase inhibitor (TKI) and CRT plus pembrolizumab, respectively, as their first treatment. Of patients who received subsequent treatment (n = 115), most received EGFR-TKIs (75 %; n = 86/115). In patients who received CRT alone as first treatment, median (95 % confidence interval) rwPFS, rwTTNTD, and OS were 6.7 (6.0-9.0), 11.4 (9.0-14.4), and 68.6 (60.9-not evaluable) months, respectively.
Conclusion: In this rw study in patients with unresectable stage III EGFR-mutated NSCLC, CRT alone was the most common first treatment and EGFR-TKIs were the most common first subsequent treatment. OS was substantial despite relatively short rwPFS, which may be attributed to subsequent EGFR-TKIs. The findings highlight the unmet need for alternative treatments in this setting.
Keywords: EGFR; Mutation frequency; Non-small cell lung cancer; Retrospective study; Treatment outcome.
Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of competing interest Myung-Ju Ahn: Advisory role: Alpha Pharmaceuticals, Amgen, AstraZeneca, Daiichi-Sankyo, Genexine, Merck, Merck Sharp & Dohme, Ono Pharmaceutical, Pfizer, Roche, Takeda, Voronoi, Yuhan; Invited speaker: Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Merck, Merck Sharp & Dohme, Roche, Takeda, and Yuhan. Steven H. Lin: Advisory council or committee: XRAD Therapeutics; Employment: MD Anderson Cancer Center; Co-founder: Seek Diagnostics; Grants or funds: Beyond Spring Pharmaceuticals, Nektar Therapeutics, STCube Pharmaceuticals; Ownership of stocks/shares: Apple, Google, Meta, Netflix, Tesla, Rivian. Cheng-Ta Yang: Advisory council or committee: AstraZeneca, Boehringer Ingelheim, Lilly, MSD, Novartis, Ono Pharmaceutical, Roche; Advisory role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Merck, Ono Pharmaceutical; Consulting fee: AstraZeneca, Boehringer Ingelheim, Lilly, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche; Invited Speaker: AstraZeneca, Boehringer Ingelheim, Lilly, MSD, Ono Pharmaceutical, Pfizer, Roche; Local PI: AstraZeneca, Boehringer Ingelheim, Pfizer. Jii Bum Lee: Nothing to disclose. Joel W. Neal: Advisory or consulting: AbbVie, Amgen, AnHeart Therapeutics, AstraZeneca, Blueprint Pharmaceuticals, Bristol Myers Squibb, D2G Oncology, Daiichi-Sankyo/AstraZeneca, Exelixis, Eli Lilly and Company, Genentech/Roche, Gilead Sciences, Iovance Biotherapeutics, Janssen, Mirati Therapeutics, Natera, Novartis, Novocure, Nuvation Bio, Sanofi/Regeneron, Summit Therapeutics, Surface Oncology, Takeda Pharmaceuticals, Turning Point Therapeutics; Grants or funds: Adaptimmune, Boehringer Ingelheim, Exelixis, Genentech/Roche, GSK, Janssen (to institution), Merck, Nektar Therapeutics, Novartis, Nuvalent, Revolution Medicines, Takeda Pharmaceuticals; Honoraria: Biomedical Learning Institute CME, Clinical Care Options CME, CME Matters, HMP Education, Medical Educator Consortium, Medscape CME, MJH Life Sciences CME, MLI Peerview CME, Prime Oncology CME, Projects in Knowledge CME, Research to Practice CME, Rockpointe CME. Kyoichi Okishio: Grants or funds: Ono Pharmaceutical. Kazumi Nishino: Advisory council or committee: AstraZeneca, Janssen Pharmaceutical K.K., Pfizer; Coordinating PI: AbbVie, AstraZeneca, Amgen, Chugai Pharmaceutical, Daiichi-Sankyo, Eizai Co. Ltd., Eli Lilly, Janssen Pharmaceutical K.K., Merck Biopharma, Merus, MSD, Novartis Pharmaceuticals, Ono Pharmaceutical, Pfizer, Sanofi K.K., Taiho Pharmaceutical, Takada Pharmaceutical; Invited Speaker: Amgen, AstraZeneca, Chugai Pharmaceutical, Daiichi-Sankyo, Eli Lilly Japan, Janssen Pharmaceutical K.K., Merck Biopharma, Mochida Pharmaceutical, MSD, Nippon Boehringer Ingelheim, Novartis Pharmaceutical, Ono Pharmaceutical, Pfizer, Takeda Pharmaceutical, Varian Medical Systems, Yuyu Teijin Medicare. Daniel Smith: Speaker, consultant, advisor: AstraZeneca. Markus Rauter: Nothing to disclose. Maria Jimenez: Consulting fees: AstraZeneca (to institution). Feruza Nasirova: Employment: AstraZeneca; Ownership of stocks/shares: AstraZeneca. YongJin Kim: Employment: AstraZeneca; Ownership of stocks/shares: AstraZeneca.
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