Author(s): Masahiro Tsuboi, M.D., Roy S. Herbst, M.D., Ph.D., Thomas John, M.B., B.S., Ph.D., Terufumi Kato, M.D., Margarita Majem, M.D., Ph.D., Christian Grohé, M.D., Jie Wang, M.D., Ph.D., Jonathan W. Goldman, M.D., Shun Lu, M.D., Wu-Chou Su, M.D., Filippo de Marinis, M.D., Frances A. Shepherd, M.D., Ki Hyeong Lee, M.D., Ph.D., Nhieu Thi Le, M.D., Arunee Dechaphunkul, M.D., Dariusz Kowalski, M.D., Ph.D., Lynne Poole, M.Sc., Ana Bolanos, M.D., Yuri Rukazenkov, M.D., Ph.D., and Yi-Long Wu, M.D. for the ADAURA Investigators*
BACKGROUND
Among patients with resected, epidermal growth factor receptor (EGFR)–mutated, stage IB to IIIA non–small-cell lung cancer (NSCLC), adjuvant osimertinib therapy, with or without previous adjuvant chemotherapy, resulted in significantly longer disease-free survival than placebo in the ADAURA trial. We report the results of the planned final analysis of overall survival.
METHODS
In this phase 3, double-blind trial, we randomly assigned eligible patients in a 1:1 ratio to receive osimertinib (80 mg once daily) or placebo until disease recurrence was observed, the trial regimen was completed (3 years), or a discontinuation criterion was met. The primary end point was investigator-assessed disease-free survival among patients with stage II to IIIA disease. Secondary end points included disease-free survival among patients with stage IB to IIIA disease, overall survival, and safety.
RESULTS
Of 682 patients who underwent randomization, 339 received osimertinib and 343 received placebo. Among patients with stage II to IIIA disease, the 5-year overall survival was 85% in the osimertinib group and 73% in the placebo group (overall hazard ratio for death, 0.49; 95.03% confidence interval [CI], 0.33 to 0.73; P<0.001). In the overall population (patients with stage IB to IIIA disease), the 5-year overall survival was 88% in the osimertinib group and 78% in the placebo group (overall hazard ratio for death, 0.49; 95.03% CI, 0.34 to 0.70; P<0.001). One new serious adverse event, pneumonia related to coronavirus disease 2019, was reported after the previously published data-cutoff date (the event was not considered by the investigator to be related to the trial regimen, and the patient fully recovered). Adjuvant osimertinib had a safety profile consistent with that in the primary analysis.
CONCLUSIONS
Adjuvant osimertinib provided a significant overall survival benefit among patients with completely resected, EGFR-mutated, stage IB to IIIA NSCLC. (Funded by AstraZeneca; ADAURA ClinicalTrials.gov number, NCT02511106.)
Author Affiliations
From the Department of Thoracic Surgery and Oncology, National Cancer Center Hospital East, Kashiwa (M.T.), the Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama (T.K.) — both in Japan; the Section of Medical Oncology, Yale School of Medicine and Yale Cancer Center, New Haven, CT (R.S.H.); the Department of Medical Oncology, Peter MacCallum Cancer Centre, and the Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia (T.J.); the Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona (M.M.); Klinik für Pneumologie, Evangelische Lungenklinik Berlin Buch, Berlin (C.G.); Cancer Hospital, Chinese Academy of Medical Sciences, Beijing (J.W.), Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai (S.L.), and Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou (Y.-L.W.) — all in China; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.W.G.); the Department of Oncology, National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Division of Thoracic Oncology, European Institute of Oncology, IRCCS, Milan (F.M.); the Department of Medical Oncology and Hematology, University Health Network, Princess Margaret Cancer Centre (F.A.S.), and Oncology Research and Development, AstraZeneca (A.B.) — both in Toronto; the Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, South Korea (K.H.L.); Ho Chi Minh City Oncology Hospital, Binh Thanh District, Ho Chi Minh City, Vietnam (N.T.L.); the Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand (A.D.); the Department of Lung Cancer and Thoracic Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (D.K.); and Oncology Biometrics (L.P.), and Oncology Research and Development (Y.R.), AstraZeneca, Cambridge, United Kingdom.
