LBA47 - Osimertinib as adjuvant therapy in patients (pts) with resected EGFR-mutated (EGFRm) stage IB-IIIA non-small cell lung cancer (NSCLC): Updated results from ADAURA

Background

Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) that potently and selectively inhibits EGFR-TKI sensitising and EGFR T790M resistance mutations. It has efficacy in EGFRm NSCLC, including in central nervous system (CNS) metastases. In the Phase III ADAURA (NCT02511106) primary analysis adjuvant osimertinib showed a significant and clinically meaningful disease-free survival (DFS) benefit vs placebo (PBO) in pts with completely resected EGFRm (ex19del/L858R) NSCLC, ± adjuvant chemotherapy (CT): stage IIꟷIIIA DFS HR, 0.17; 99.06% CI, 0.11, 0.26; p<0.0001; stage IBꟷIIIA DFS HR, 0.20; 99.12% CI 0.14, 0.30; p<0.0001. We report updated exploratory analyses of DFS and recurrence patterns after 2 yrs added follow up.

Methods

Eligible pts (aged ≥18 yrs [≥20 in Japan/Taiwan], WHO PS 0/1, completely resected EGFRm stage IBꟷIIIA [AJCC 7^th edition] NSCLC; adjuvant CT allowed) were randomised 1:1 to osimertinib 80 mg once daily or PBO for up to 3 yrs. Primary endpoint: investigator-assessed DFS in stage IIꟷIIIA. Secondary endpoints: DFS in stage IBꟷIIIA, overall survival and safety. Patterns of recurrence and CNS DFS were pre-specified exploratory endpoints. Data cut-off: 11 April 2022.

Results

Globally, 682 pts were randomised; osimertinib n=339, PBO n=343. In this updated analysis, in pts with stage IIꟷIIIA disease DFS HR was 0.23 (95% CI 0.18, 0.30; 242/470 events; 51% maturity); 3-yr DFS rate was 84% with osimertinib vs 34% with PBO. In the overall population (stage IBꟷIIIA) DFS HR was 0.27 (95% CI 0.21, 0.34; 305/682 events); 3-yr DFS rate was 85% with osimertinib vs 44% with PBO. In the osimertinib arm, fewer pts experienced local/regional and distant recurrence vs PBO. CNS DFS HR was 0.24 (95% CI 0.14, 0.42; 63/470 events) in stage IIꟷIIIA. The long-term safety profile remains consistent with the known profile of osimertinib.

Conclusions

With 2 yrs further follow-up, a continued DFS benefit was sustained with osimertinib vs PBO, consistent with the primary analysis. These mature data reinforce adjuvant osimertinib as standard of care for pts with EGFRm stage IB–‍IIIA NSCLC after complete tumour resection and adjuvant CT, when indicated.

Clinical trial identification

NCT02511106.

Editorial acknowledgement

The authors would like to acknowledge Rachel Gater, PhD, of Ashfield MedComms, an Inizio Company, for medical writing support that was funded by AstraZeneca in accordance with Good Publications Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

M. Tsuboi: Financial Interests, Advisory Role: AstraZeneca, Merck Sharp & Dohme, Novartis, Chugai Pharmaceutical Co. Ltd.; Financial Interests, Other, Research Support: Boehringer Ingelheim, Merck Sharp & Dohme, AstraZeneca, Ono Pharmaceuticals Co. Ltd., Bristol-Myers Squibb, Eli Lilly, Novartis, MIRXES Japan; Financial Interests, Invited Speaker: Johnson & Johnson, AstraZeneca, Eli Lilly, Chugai Pharmaceutical Co. Ltd., Taiho Pharma, Medtronic Japan Co., Ltd., Ono Pharmaceutical Co. Ltd., Merck Sharp & Dohme, Bristol-Myers Squibb, Teijin Pharma. Y. Wu: Financial Interests, Advisory Role: AstraZeneca, Boehringer Ingelheim, Novartis, Takeda; Financial Interests, Other, Research Support: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Hengrui, Roche; Financial Interests, Other, Honoraria: AstraZeneca, Beigen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche, Sanofi. C. Grohe: Financial Interests, Advisory Role: AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme; Financial Interests, Other, Travel Fees: Boehringer Ingelheim; Financial Interests, Speaker’s Bureau: AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme. T. John: Financial Interests, Advisory Role: Pfizer, AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Ignyta, Novartis, Bayer. M. Majem Tarruella: Financial Interests, Advisory Role: Roche, AstraZeneca; Financial Interests, Other, Research Support: Bristol-Myers Squibb, Roche, AstraZeneca; Financial Interests, Other, Honoraria: Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca, Roche, Kyowa Kyrin, Pierre Fabre, Takeda, Bayer, Amgen Inc.. J. Wang: Financial Interests, Other, Honoraria: AstraZeneca, Beigne, Boehringer Ingelheim, Merck Sharp & Dohme. T. Kato: Financial Interests, Advisory Role: AstraZeneca, Amgen Inc., Chugai Pharmaceuticals Co., Ltd., Eli Lilly, Merck Serono, Merck Sharp & Dohme, Pfizer, Daiichi-Sankyo; Financial Interests, Speaker’s Bureau: AstraZeneca, Amgen Inc., Chugai Pharmaceutical Co., Ltd., Eli Lilly, Merck Serono, Merck Sharp & Dohme, Pfizer, Bristol-Myers Squibb, Novartis, Taiho Pharmaceutical, Boehringer Ingelheim, Roche; Financial Interests, Full or part-time Employment, Spouse: Eli Lilly; Financial Interests, Other, Research Support: AstraZeneca, Amgen Inc., Chugai Pharmaceutical Co., Ltd., Eli Lilly, Merck Serono, Merck Sharp & Dohme, Pfizer, Novartis, AbbieVie Inc., Regeneron. J.W. Goldman: Financial Interests, Other, Research Support: Advaxis, Array, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Genentech, G1 Therapeutics, Merck, Pfizer; Financial Interests, Other, Travel Fees: AstraZeneca; Financial Interests, Other, Honoraria: AstraZeneca, Bristol-Myers Squibb, Genentech, Pfizer. S. Kim: Financial Interests, Advisory Role: AstraZeneca, Boehringer Ingelheim, Novartis, Eli Lilly, Roche, Bristol-Myers Squibb; Financial Interests, Other, Research Support: AstraZeneca, Boehringer Ingelheim, Novartis, Eli Lilly, Yuhan. G. Mukhametshina: Financial Interests, Invited Speaker: Roche, AstraZeneca, EISAI; Financial Interests, Principal Investigator: Merck Sharp & Dohme, AstraZeneca. F. de Marinis: Financial Interests, Speaker’s Bureau: AstraZeneca, Bristol-Myers Squibb, Novartis, Pfizer, Takeda, Roche, MSD, X-Covery. F.A. Shepherd: Financial Interests, Stocks/Shares: AstraZeneca. D. Urban: Financial Interests, Advisory Role: AstraZeneca, Merck Sharp & Dohme; Financial Interests, Other, Honoraria: Roche, Merck Serono, Merck Sharp & Dohme, Takeda, AstraZeneca, Rhenium Oncotest, Ltd., Bristol-Myers Squibb. M. Stachowiak: Financial Interests, Full or part-time Employment: AstraZeneca. A.L. Bolanos: Financial Interests, Full or part-time Employment: AstraZeneca. X. Huang: Financial Interests, Full or part-time Employment: AstraZeneca; Financial Interests, Stocks/Shares: AstraZeneca. R.S. Herbst: Financial Interests, Advisory Board: AstraZeneca, Bolt Biotherapeutics, Candel Therapeutics, Inc., Checkpoint Therapeutics, Cybrexa Therapeutics, EMD Serono, I-Mab Biopharma, Immune-Onc Therapeutics, Inc., Immunocore, Ocean Biomedical, Inc., Revelar Biotherapeutics, Inc, Ribbon Therapeutics, Xencor, Inc; Financial Interests, Other, Consulting: Bristol-Myers Squibb, DynamiCure Biotechnology, LLC, eFFECTOR Therapeutics, Inc, Eli Lilly and Company, Genentech, Gilead, HiberCell, Inc., Janssen, Johnson and Johnson, Loxo Oncology, Mirati Therapeutics, NextCure, Novartis, Oncocyte Corp, Oncternal Therapeutics, Pfizer, Regeneron Pharmaceuticals, Roche, Sanofi; Financial Interests, Other, Research Support: AstraZeneca, Eli Lilly and Company, Genentech/Roche, Merck and Company; Financial Interests, Member of the Board of Directors: Immunocore, Junshi Pharmaceuticals; Financial Interests, Leadership Role: American Association for Cancer Research, International Association for the Study of Lung Cancer, Society for Immunotherapy of Cancer, Southwest Oncology Group. All other authors have declared no conflicts of interest.