Yi-Long Wu1, Masahiro Tsuboi1, Jie He1, Thomas John1, Christian Grohe1, Margarita Majem1, Jonathan W Goldman1, Konstantin Laktionov1, Sang-We Kim1, Terufumi Kato1, Huu-Vinh Vu1, Shun Lu1, Kye-Young Lee1, Charuwan Akewanlop1, Chong-Jen Yu1, Filippo de Marinis1, Laura Bonanno1, Manuel Domine1, Frances A Shepherd1, Lingmin Zeng1, Rachel Hodge1, Ajlan Atasoy1, Yuri Rukazenkov1, Roy S Herbst1. 1. From the Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, and Guangdong Academy of Medical Sciences, Guangzhou (Y.-L.W.), the Thoracic Surgery Department, National Cancer Center-National Clinical Research Center for Cancer-Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (J.H.), and the Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai (S.L.) - all in China; the Department of Thoracic Surgery and Oncology, National Cancer Center Hospital East, Kashiwa (M.T.), and the Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama (T.K.) - both in Japan; the Department of Medical Oncology, Austin Health, Melbourne, VIC, Australia (T.J.); the Department of Respiratory Diseases, Evangelische Lungenklinik, Berlin (C.G.); the Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona (M.M.), and the Department of Oncology, Hospital Universitario Fundación Jiménez Díaz, Madrid (M.D.); the David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J.W.G.); the Center of Innovative Technologies and Oncology, N.N. Blokhin Russian Cancer Center, Russian Academy of Medical Sciences, Moscow (K.L.); the Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine (S.-W.K.), and the Precision Medicine Lung Cancer Center, Konkuk University Medical Center (K.-Y.L.) - both in Seoul, South Korea; the Department of Thoracic Surgery, Cho Ray Hospital, Ho Chi Minh City, Vietnam (H.-V.V.); the Division of Medical Oncology, Faculty of Medicine, Siriraj Hospital, Bangkok, Thailand (C.A.); the Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (C.-J.Y.); the Division of Thoracic Oncology, European Institute of Oncology, IRCCS, Milan (F.M.), and Medical Oncology 2, Istituto Oncologico Veneto, IRCCS, Padua (L.B.) - both in Italy; the Department of Medical Oncology and Hematology, University Health Network, Princess Margaret Cancer Centre and the University of Toronto, Toronto (F.A.S.); Late Oncology Statistics, AstraZeneca, Gaithersburg, MD (L.Z.); Late Oncology Statistics (R.H.) and Oncology Research and Development (A.A., Y.R.), AstraZeneca, Cambridge, United Kingdom; and Section of Medical Oncology, Yale School of Medicine and Yale Cancer Center, New Haven, CT (R.S.H.).
Abstract
BACKGROUND: Osimertinib is standard-of-care therapy for previously untreated epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC). The efficacy and safety of osimertinib as adjuvant therapy are unknown. METHODS: In this double-blind, phase 3 trial, we randomly assigned patients with completely resected EGFR mutation-positive NSCLC in a 1:1 ratio to receive either osimertinib (80 mg once daily) or placebo for 3 years. The primary end point was disease-free survival among patients with stage II to IIIA disease (according to investigator assessment). The secondary end points included disease-free survival in the overall population of patients with stage IB to IIIA disease, overall survival, and safety. RESULTS: A total of 682 patients underwent randomization (339 to the osimertinib group and 343 to the placebo group). At 24 months, 90% of the patients with stage II to IIIA disease in the osimertinib group (95% confidence interval [CI], 84 to 93) and 44% of those in the placebo group (95% CI, 37 to 51) were alive and disease-free (overall hazard ratio for disease recurrence or death, 0.17; 99.06% CI, 0.11 to 0.26; P<0.001). In the overall population, 89% of the patients in the osimertinib group (95% CI, 85 to 92) and 52% of those in the placebo group (95% CI, 46 to 58) were alive and disease-free at 24 months (overall hazard ratio for disease recurrence or death, 0.20; 99.12% CI, 0.14 to 0.30; P<0.001). At 24 months, 98% of the patients in the osimertinib group (95% CI, 95 to 99) and 85% of those in the placebo group (95% CI, 80 to 89) were alive and did not have central nervous system disease (overall hazard ratio for disease recurrence or death, 0.18; 95% CI, 0.10 to 0.33). Overall survival data were immature; 29 patients died (9 in the osimertinib group and 20 in the placebo group). No new safety concerns were noted. CONCLUSIONS: In patients with stage IB to IIIA EGFR mutation-positive NSCLC, disease-free survival was significantly longer among those who received osimertinib than among those who received placebo. (Funded by AstraZeneca; ADAURA ClinicalTrials.gov number, NCT02511106.).
BACKGROUND: Osimertinib is standard-of-care therapy for previously untreated epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC). The efficacy and safety of osimertinib as adjuvant therapy are unknown. METHODS: In this double-blind, phase 3 trial, we randomly assigned patients with completely resected EGFR mutation-positive NSCLC in a 1:1 ratio to receive either osimertinib (80 mg once daily) or placebo for 3 years. The primary end point was disease-free survival among patients with stage II to IIIA disease (according to investigator assessment). The secondary end points included disease-free survival in the overall population of patients with stage IB to IIIA disease, overall survival, and safety. RESULTS: A total of 682 patients underwent randomization (339 to the osimertinib group and 343 to the placebo group). At 24 months, 90% of the patients with stage II to IIIA disease in the osimertinib group (95% confidence interval [CI], 84 to 93) and 44% of those in the placebo group (95% CI, 37 to 51) were alive and disease-free (overall hazard ratio for disease recurrence or death, 0.17; 99.06% CI, 0.11 to 0.26; P<0.001). In the overall population, 89% of the patients in the osimertinib group (95% CI, 85 to 92) and 52% of those in the placebo group (95% CI, 46 to 58) were alive and disease-free at 24 months (overall hazard ratio for disease recurrence or death, 0.20; 99.12% CI, 0.14 to 0.30; P<0.001). At 24 months, 98% of the patients in the osimertinib group (95% CI, 95 to 99) and 85% of those in the placebo group (95% CI, 80 to 89) were alive and did not have central nervous system disease (overall hazard ratio for disease recurrence or death, 0.18; 95% CI, 0.10 to 0.33). Overall survival data were immature; 29 patients died (9 in the osimertinib group and 20 in the placebo group). No new safety concerns were noted. CONCLUSIONS: In patients with stage IB to IIIA EGFR mutation-positive NSCLC, disease-free survival was significantly longer among those who received osimertinib than among those who received placebo. (Funded by AstraZeneca; ADAURA ClinicalTrials.gov number, NCT02511106.).
Authors: Joel W Neal; Daniel B Costa; Alona Muzikansky; Joseph B Shrager; Michael Lanuti; James Huang; Kavitha J Ramachandran; Deepa Rangachari; Mark S Huberman; Zofia Piotrowska; Mark G Kris; Christopher G Azzoli; Lecia V Sequist; Jamie E Chaft Journal: JCO Precis Oncol Date: 2021-02-01