LAUSR

Abstract Background Data on the frequency of EGFR mutations in patients (pts) with NSCLC potentially eligible for adjuvant therapy are limited. Osimertinib, a 3rd-generation, irreversible, oral EGFR-tyrosine kinase inhibitor (TKI), potently and selectively inhibits both EGFR-TKI sensitising (EGFRm) and EGFR T790M mutations, and has shown efficacy in the CNS. The ADAURA study (NCT02511106) will assess osimertinib as adjuvant therapy in early-stage NSCLC after complete resection. Here we report frequency of the most common EGFR activating mutations from pts screened for ADAURA. Methods ADAURA is a Phase III, double-blind, randomised, placebo-controlled study assessing efficacy and safety of osimertinib vs placebo in adult pts with mainly non-squamous histology, stage IB–IIIA EGFRm NSCLC, following complete tumour resection, without or after adjuvant chemotherapy. At screening, EGFR mutations associated with EGFR-TKI sensitivity (ex19del, L858R), alone or in combination with exon 20 insertion, G719X, S768I, T790M or L861Q were centrally assessed from resected tumour samples using the cobas® EGFR Mutation Test (Roche Molecular Systems). Some pts may have been pre-screened for EGFR mutations using local tests. Results In total, 2447 pts were screened. Median age was 63 years (range 23–88), 54% were female, and 61% were non-Asian. At screening, 1087 (44%) pts were EGFR mutation positive; 110/2447 (4%) pts had an unknown/unevaluable test result. Of pts EGFR mutation positive, the most common mutations were ex19del and L858R in 572 (53%) and 458 (42%) pts, respectively; exon 20 insertion, G719X, T790M, S768I, and L861Q mutations occurred in 28 (3%), 24 (2%), 19 (2%), 11 (1%) and 8 (1%) pts, respectively. Mutations occurred alone or in combination. A higher proportion of EGFR mutation positive pts were Asian vs non-Asian (681 [63%] vs 402 [37%]; 4 pts missing) and female vs male (755 [69%] vs 331 [30%]; 1 pt missing). Conclusions This analysis shows a high prevalence of EGFRm mutations in Asian and female pts with stage IB–IIIA NSCLC following complete resection, which is consistent with the advanced setting. International screening for EGFR mutations in the adjuvant setting should be considered. Clinical trial identification NCT02511106. Editorial acknowledgement Natalie Griffiths, PhD, from iMed Comms, an Ashfield Company; funded by AstraZeneca. Legal entity responsible for the study AstraZeneca. Funding AstraZeneca. Disclosure M. Tsuboi: Research grant / Funding (institution): Boehringer Ingelheim Japan; Honoraria (self): Johnson & Johnson Japan, AstraZeneca KK, Eli Lilly Japan, Boehringer Ingelheim Japan, Daiichi-Sankyo, Chugai Pharmaceutical, Taiho Pharma, Covidien Japan, Ono Pharmaceutical, Merck Sharp & Dohme, Bristol-Myers Squibb KK, Teijin Pharma. R.S. Herbst: Advisory / Consultancy, Consulting: AbbVie Pharmaceuticals, ARMO Biosciences, AstraZeneca, Biodesix, Bristol-Myers Squibb, Eli Lilly, EMD Serrano, Genentech/Roche, Genmab, Heat Biologics, Halozyme, Loxo Oncology, Merck & Company, Nektar, NextCure, Novartis, Pfizer, Sanofi, Seattle Genetics,; Research grant / Funding (institution): AstraZeneca, Eli Lilly, Merck; Advisory / Consultancy, Scientific Advisory Boards: Neon Therapeutics, Infinity Pharmaceuticals, NextCure; Leadership role, Board Member (non-executive/independent): Junshi Pharmaceuticals. T. John: Advisory / Consultancy: Roche, Bristol-Myers Squibb, Merck, Ignyta, AstraZeneca, Takeda. M. Majem: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck Sharp & Dohme; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy: Tesaro; Speaker Bureau / Expert testimony: Hellsin; Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre; Speaker Bureau / Expert testimony: Amgen. J.W. Goldman: Research grant / Funding (institution): AbbVie; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck; Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (institution): AstraZeneca. S. Novello: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Roche, Merck Sharp & Dohme, Takeda, Pfizer, AbbVie, AstraZeneca, Celgene. D. Urban: Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca. C. Akewanlop: Travel / Accommodation / Expenses: Amgen, AstraZeneca, Roche. D. Kowalski: Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim. D. Marmol: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Marotti: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. G. Laus: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. Y. Wu: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca, Roche; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self): Eli Lilly, Pfizer, Merck Sharp & Dohme, Bristol-Myers Squibb. All other authors have declared no conflicts of interest.