296P - 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.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

Y. Wu: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Novartis, Takeda; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Hengrui, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Merck Sharp & Dohme, Pfizer, Roche, Sanofi. M. Tsuboi: Financial Interests, Personal, Invited Speaker, Lecture: Johnson & Johnson Japan; Financial Interests, Personal, Advisory Board, Lectures, Advisory boards: AstraZeneca KK, Chugai Pharmaceutical Co., Ltd., MSD; Financial Interests, Personal, Invited Speaker, Lectures: Eli Lilly Japan, Bristol Myers Squibb KK, Teijin Pharma, Taiho Pharma, Medtronic Japan, ONO Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board, Advisory boards: Novartis; Financial Interests, Personal, Invited Speaker: Daiichi-Sankyo company limited, MSD, AstraZeneca, Novartis; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim Japan, MSD, AstraZeneca KK, Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb KK, Novartis; Financial Interests, Institutional, Invited Speaker: Eli Lilly Japan. C. Grohe: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel fees: Boehringer Ingelheim; speaker’s bureau: AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme. T. John: Financial Interests, Personal, Invited Speaker, Speaker tour Vietnam: Astra Zeneca; Financial Interests, Personal, Invited Speaker, CTIO: Merck Sharp Dohme; Financial Interests, Personal, Advisory Board: BMS, Astra Zeneca, Bayer, Specialised Therapeutics; Financial Interests, Institutional, Advisory Board: Roche, Novartis, Pfizer, Amgen, Takeda, PharmaMar. M. Majem Tarruella: Financial Interests, Personal, Advisory Role: Roche, AstraZeneca; Financial Interests, Personal, Research Grant: Bristol Myers Squibb, Roche, AstraZeneca; Financial Interests, Personal, Other, Honoraria: Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca, Roche, Kyowa Kyrin, Pierre Fabre, Takeda, Bayer, Amgen Inc. J. Wang: Financial Interests, Personal, Other, Honararia: AstraZeneca, Beigne, Boehringer Ingelheim, Merck Sharp & Dohme. T. Kato: Financial Interests, Personal, Advisory Board, speaker, consultancy: AstraZeneca, Eli Lilly, Merck Biopharma, MSD; Financial Interests, Personal, Advisory Board, speaker: Pfizer; Financial Interests, Personal, Other, consultancy: Daiichi-Sankyo, Takeda, Taiho; Financial Interests, Personal, Other, consultancy, speaker: Chugai; Financial Interests, Personal, Invited Speaker: Ono, Novartis; Financial Interests, Personal, Advisory Board: Beigene, Glaxo; Financial Interests, Personal, Full or part-time Employment, Family member: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Chugai, MSD, Pfizer, AstraZeneca, Eli Lilly, Abbvie, Regeneron, Novartis, Amgen, Merck Biophama, Haihe Biopharma, Blueprint Medicines, Turning Point. J.W. Goldman: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Genentech, Eli Lilly, Janssen, AbbVie; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Genentech, Eli Lilly, Janssen, BMS, AbbVie. K. Sang-We: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Novartis, Eli Lilly and Company, Roche, Bristol Myers Squibb; Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim, Novartis, Eli Lilly and Company, Yuhan. G. Mukhametshina: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, EISAI; Financial Interests, Personal, Principal Investigator: Merck Sharp & Dohme, AstraZeneca. F. de Marinis: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Novartis, Pfizer, Takeda, Roche, MSD, X-Covery. F.A. Shepherd: Financial Interests, Personal, Stocks/Shares: AstraZeneca. D. Urban: Financial Interests, Personal, Advisory Role: AstraZeneca, Merck Sharp & Dohme; Financial Interests, Personal, Other, Honoraria: Roche, Merck Serono, Merck Sharp & Dohme, Takeda, AstraZeneca, Rhenium Oncotest, Ltd., Bristol Myers Squibb. M. Stachowiak: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. A. Bolanos: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. X. Huang: Financial Interests, Personal, Full or part-time Employment: AstraZeneca,; Financial Interests, Personal, Stocks/Shares: AstraZeneca. R.S. Herbst: Financial Interests, Personal, Advisory Role: AstraZeneca, Bolt Biotherapeutics, Bristol Myers Squibb, Candel Therapeutics, Inc., Checkpoint Therapeutics, Cybrexa Therapeutics, DynamiCure Biotechnology, LLC, eFFECTOR Therapeutics, Inc., Eli Lilly and Company, EMD Serono, Genentech, Gilead, HiberCell,; Financial Interests, Personal, Research Grant: AstraZeneca, Eli Lilly and Company, Genentech, Merck Sharp & Dohme; Financial Interests, Personal, Leadership Role: American Association for Cancer Research, International Association for the Study of Lung Cancer, Society for Immunotherapy of Cancer, Southwest Oncology Group; Financial Interests, Personal, Advisory Board: Immunocore, Junshi Pharmaceuticals. All other authors have declared no conflicts of interest.