PMID- 37236398 OWN - NLM STAT- MEDLINE DCOM- 20230823 LR - 20230824 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 18 IP - 9 DP - 2023 Sep TI - Three-Year Safety, Tolerability, and Health-Related Quality of Life Outcomes of Adjuvant Osimertinib in Patients With Resected Stage IB to IIIA EGFR-Mutated NSCLC: Updated Analysis From the Phase 3 ADAURA Trial. PG - 1209-1221 LID - S1556-0864(23)00574-9 [pii] LID - 10.1016/j.jtho.2023.05.015 [doi] AB - INTRODUCTION: In ADAURA, adjuvant osimertinib significantly improved disease-free survival versus placebo in resected stage IB to IIIA EGFR-mutated NSCLC. We report in-depth analyses of three-year safety, tolerability, and health-related quality of life (HRQoL) from ADAURA. METHODS: Patients were randomized 1:1 to osimertinib 80 mg or placebo once daily for up to 3 years. Safety assessments were performed at baseline, week 2, week 4, week 12, and every 12 weeks until treatment completion or discontinuation, and 28 days after treatment was stopped. The SF-36 survey measured HRQoL at baseline, week 12, week 24, and every 24 weeks until recurrence, treatment completion or discontinuation. Data cutoff: April 11, 2022. RESULTS: Safety and HRQoL analysis sets: osimertinib, n = 337 and n = 339; placebo, n = 343 each. Median (range) total exposure duration was longer with osimertinib versus placebo: 35.8 (0-38) versus 25.1 (0-39) months. Most adverse events (AEs) were first reported within 12 months of starting treatment (osimertinib 97%, placebo 86%). AEs leading to dose reduction, interruption or discontinuation were reported in 12%, 27% and 13% respectively of patients with osimertinib; 1%, 13% and 3% with placebo. Stomatitis and diarrhea were the most common AEs leading to osimertinib dose reduction or interruption; interstitial lung disease was the most common leading to osimertinib discontinuation (per protocol). There were no differences in time to deterioration for SF-36 physical, mental component summaries between osimertinib and placebo. CONCLUSIONS: No new safety signals were reported and HRQoL was maintained with 3 years of adjuvant osimertinib treatment. Combined with significant efficacy benefit, these data further support adjuvant osimertinib in stage IB to IIIA EGFR-mutated NSCLC. CI - Copyright (c) 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. FAU - John, Thomas AU - John T AD - Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia. Electronic address: Tom.John@petermac.org. FAU - Grohe, Christian AU - Grohe C AD - Klinik fur Pneumologie - Evangelische Lungenklinik Berlin Buch, Berlin, Germany. FAU - Goldman, Jonathan W AU - Goldman JW AD - David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California. FAU - Shepherd, Frances A AU - Shepherd FA AD - Department of Medical Oncology and Hematology, University Health Network, Princess Margaret Cancer Centre and the University of Toronto, Toronto, Ontario, Canada. FAU - de Marinis, Filippo AU - de Marinis F AD - Thoracic Oncology Division, European Institute of Oncology (IEO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy. FAU - Kato, Terufumi AU - Kato T AD - Department of Thoracic Oncology, Kanagawa Cancer Center, Asahi Ward, Yokohama, Japan. FAU - Wang, Qun AU - Wang Q AD - Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China. FAU - Su, Wu-Chou AU - Su WC AD - Department of Oncology, National Cheng Kung University, Tainan, Taiwan. FAU - Choi, Jin Hyuk AU - Choi JH AD - Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Republic of Korea. FAU - Sriuranpong, Virote AU - Sriuranpong V AD - Division of Medical Oncology, Faculty of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, Thailand. FAU - Melotti, Barbara AU - Melotti B AD - Division of Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. FAU - Fidler, Mary J AU - Fidler MJ AD - Hematology, Oncology and Cell Therapy, Department of Medicine, Rush University Medical Center, Chicago, Illinois. FAU - Chen, Jun AU - Chen J AD - Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China. FAU - Albayaty, Muna AU - Albayaty M AD - Oncology Research & Development, AstraZeneca, Cambridge, United Kingdom. FAU - Stachowiak, Marta AU - Stachowiak M AD - Late Oncology Research & Development, AstraZeneca, Warsaw, Poland. FAU - Taggart, Sarah AU - Taggart S AD - Oncology Biometrics, AstraZeneca, Cambridge, United Kingdom. FAU - Wu, Yi-Long AU - Wu YL AD - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People's Republic of China. FAU - Tsuboi, Masahiro AU - Tsuboi M AD - Department of Thoracic Surgery and Oncology, National Cancer Center Hospital East, Kashiwa, Japan. FAU - Herbst, Roy S AU - Herbst RS AD - Medical Oncology, Yale School of Medicine and Yale Cancer Center, New Haven, Connecticut. FAU - Majem, Margarita AU - Majem M AD - Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. LA - eng SI - ClinicalTrials.gov/NCT02511106 PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230524 PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (Aniline Compounds) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - 3C06JJ0Z2O (osimertinib) RN - 0 (Protein Kinase Inhibitors) SB - IM MH - Humans MH - Aniline Compounds/adverse effects MH - *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/chemically induced MH - ErbB Receptors/genetics/therapeutic use MH - *Lung Neoplasms/drug therapy/genetics/chemically induced MH - Mutation MH - Protein Kinase Inhibitors/therapeutic use MH - Quality of Life OTO - NOTNLM OT - Adjuvant OT - EGFR OT - Non-small cell lung cancer OT - Osimertinib OT - Safety EDAT- 2023/05/27 09:42 MHDA- 2023/08/22 06:42 CRDT- 2023/05/26 19:26 PHST- 2023/03/26 00:00 [received] PHST- 2023/05/19 00:00 [revised] PHST- 2023/05/19 00:00 [accepted] PHST- 2023/08/22 06:42 [medline] PHST- 2023/05/27 09:42 [pubmed] PHST- 2023/05/26 19:26 [entrez] AID - S1556-0864(23)00574-9 [pii] AID - 10.1016/j.jtho.2023.05.015 [doi] PST - ppublish SO - J Thorac Oncol. 2023 Sep;18(9):1209-1221. doi: 10.1016/j.jtho.2023.05.015. Epub 2023 May 24.