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Updated: May 9, 2025
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
EGFR mutation testing across the osimertinib clinical program
Marie Laure Murat-Onana1, Suresh S Ramalingam2, Pasi A Jänne3
1Precision Medicine & Biosamples, AstraZeneca, Cambridge, UK.
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.
Insights
Most tissue samples are adequate for EGFR testing in non-small cell lung cancer (NSCLC). Optimizing pre-analytic variables and tissue sampling is crucial for improving EGFR mutation test success rates.
Area of Science:
- Oncology
- Molecular Diagnostics
- Cancer Biomarkers
Background:
- Epidermal Growth Factor Receptor (EGFR) mutations are key drivers in non-small cell lung cancer (NSCLC).
- EGFR-tyrosine kinase inhibitors (TKIs), such as osimertinib, have transformed NSCLC treatment.
- Accurate and early identification of EGFR mutations is critical for effective patient management.
Purpose of the Study:
- To analyze EGFR mutation tissue testing data from clinical trials of osimertinib in NSCLC.
- To identify challenges and factors affecting the success of EGFR mutation testing.
- To support best practices for EGFR mutation testing in NSCLC.
Main Methods:
- Pooled analysis of central Cobas® EGFR Mutation Test data from nine global osimertinib NSCLC clinical trials.
- Evaluation of specimen adequacy and test validity based on specimen type, disease stage, and geographical region.
- Analysis of reasons for testing inadequacy, including insufficient tumor content and tissue volume.
Main Results:
- Out of 4,864 biopsies and 2,402 resections, 91% were adequate for testing.
- Biopsies showed 12% inadequacy (mainly insufficient tumor/tissue), while resections had 3% inadequacy.
- Testing inadequacy varied by disease stage, being higher in advanced/metastatic settings and unresectable stage III.
- Test success rates for adequate specimens ranged from 93% to 99%.
Conclusions:
- The majority of tissue specimens are suitable for EGFR mutation testing.
- Insufficient tissue or tumor content are primary reasons for testing inadequacy, particularly in biopsies and advanced disease stages.
- Optimizing pre-analytic variables and tissue sampling techniques is essential to enhance EGFR testing success rates in NSCLC.
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