EGFR mutation testing across the osimertinib clinical program

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.