EGFR mutation testing across the osimertinib clinical program
- PMID: 40311309
- DOI: 10.1016/j.lungcan.2025.108549
EGFR mutation testing across the osimertinib clinical program
Abstract
Objectives: EGFR-tyrosine kinase inhibitors, including osimertinib, have revolutionized EGFR-mutated non-small cell lung cancer (NSCLC) treatment; therefore, early identification of EGFR mutations is essential. We report post-hoc analyses of pooled EGFR mutation tissue testing across osimertinib clinical trials, highlighting testing challenges and supporting best practice.
Materials and methods: Pooled central Cobas® EGFR Mutation Test data from nine global osimertinib NSCLC clinical trials were analyzed by specimen type, disease stage, and geographical region for specimen adequacy for testing and valid test results.
Results: Across 4,864 biopsies and 2,402 resections, 91% were adequate for testing, of which 95% of biopsies and 99% of resections had valid test results. Of biopsies, 12% were inadequate for testing (mainly due to insufficient tumor content [42%] and insufficient tissue volume [35%]) and 3% of resections were inadequate (insufficient tumor content [55%] and incorrect specimen preparation [12%]). Inadequacy varied by disease stage, from 3% in resectable stage IA2-IIIA to 10%-15% in first and second/later-line advanced/metastatic settings, and 16% in unresectable stage III. Test success rates among adequate specimens ranged from 93% (unresectable stage III) to 99% (resectable stage IA2-IIIA). Data were similar by geography.
Discussion: Most tissue specimens were adequate for EGFR testing. Inadequacy was commonly due to insufficient tissue volume or tumor content and higher in biopsies versus resections, and unresectable stage III and first-line advanced/metastatic versus other disease stages. Based on these controlled trial data, pre-analytic variables of tissue specimens are a major driver of testing success; hence maintaining optimal conditions from sample collection to biomarker analysis, as well as improving tissue-sampling techniques is critical to increase testing success rates.
Trial registration numbers: NCT01802632, NCT02094261, NCT02151981, NCT02296125, NCT04035486, NCT02511106, NCT05120349, NCT03521154, NCT04351555.
Keywords: EGFR mutation testing; EGFR mutations; Non-small cell lung cancer; Osimertinib.
Copyright © 2025. Published by Elsevier B.V.
Conflict of interest statement
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marie Laure Murat-Onana is an employee of AstraZeneca and holds stock in AstraZeneca. Suresh S. Ramalingam reports research grants from AstraZeneca, Bristol Myers Squibb, Merck, and Pfizer and reports participation on a data safety monitoring board for Janssen and Arcus. Pasi A. Jänne reports consulting fees from AbbVie, AstraZeneca, Biocartis, Boehringer-Ingelheim, Chugai Pharmaceuticals, Daiichi Sankyo, Duality Biologics, Eli Lilly and Company, Frontier Medicines, Hongyun Biotechnology, Ignyta, Loxo Oncology, Merus, Mirati Therapeutics, Monte Rosa, Novartis, Pfizer, PUMA, Roche/Genentech, Sanofi, Transcenta, Scorpion Therapeutics, SFJ Pharmaceuticals, Silicon Therapeutics, Takeda Oncology, and Voronoi; research grants from Astellas Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Daiichi Sankyo, Eli Lilly and Company, Takeda Oncology, and PUMA; co-inventor on a DFCI owned patent on EGFR mutations licensed to Lab Corp and reports post marketing royalties from DFCI owned intellectual property on EGFR mutations licensed to Lab Corp. Jhanelle E. Gray reports research grants (to institution) from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Genentech, G1 Therapeutics, Ludwig Institute of Cancer Research, Merck & Co., Novartis, and Pfizer; consulting fees and honoraria from AbbVie, AstraZeneca, Blueprint Medicines, EMD Serono, Gilead Sciences, Janssen Scientific Affairs, LLC., Jazz Pharmaceuticals, Loxo Oncology, Inc., Merck & Co., Novartis, OncoCyte Biotechnology, Spectrum ODAC, Takeda, and Triptych Health Partners; participation on a data safety monitoring board for AbbVie, AstraZeneca, Blueprint Medicines, Daiichi Sankyo, EMD Serono, Gilead Sciences, IDEOlogy Health, Janssen Scientific Affairs, LLC., Jazz Pharmaceuticals, Loxo Oncology, Inc., Merck & Co., Novartis, OncoCyte Biotechnology, Spectrum ODAC, Takeda, and Triptych Health Partners; chair for SWOG Lung Committee and ASCO Education Committee; board of directors member for IASLC and employment for Moffitt Cancer Center. Myung-Ju Ahn reports honoraria and payment for expert testimony from AstraZeneca, Roche, Merck Sharp & Dohme, Merck, Takeda, Ono Pharmaceutical, Novartis, Lilly, Amgen, and Yuhan; payment for expert testimony Alpha pharmaceuticals. Tom John reports consulting fees (to institution) from Bristol Myers Squibb, AstraZeneca, Amgen, Roche, Pfizer, Takeda, Boehringer Ingelheim, MSD, Merck, Puma, Specialised Therapeutics, Gilead, Seagen, and Johnson and Johnson; honoraria from AstraZeneca, and Merck Sharp & Dohme and support for attending meetings and/or travel from AstraZeneca. Yasushi Yatabe reports research grants (to institution) from ArcherDx, Chugai Pharmaceutical, Thermo Fischer Science, and Konika Minolta; speakers bureaus for AbbVie Inc., Amgen, AstraZeneca, Agilent/Dako, Chugai Pharmaceutical, Daiichi-Sankyo, Merck BioPharma, Merck Sharp & Dohme, and Ono Pharmaceutical; participation on a data safety monitoring board from AbbVie Inc., Amgen, AstraZeneca, Chugai Pharmaceutical, Daiichi-Sankyo, Merck Sharp & Dohme and Novartis. Xiangning Huang, Yuri Rukazenkov, Helen Brown and Xiaocheng Li-Sucholeiki report employment for AstraZeneca and hold stock in AstraZeneca. Manana Javey reports employment for Roche Diagnostics and holds stock in Roche Diagnostics. COBAS is a trademark of Roche.
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