PMID- 33721611 OWN - NLM STAT- MEDLINE DCOM- 20210621 LR - 20210621 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 154 DP - 2021 Apr TI - Safety and efficacy of first-line dacomitinib in Asian patients with EGFR mutation-positive non-small cell lung cancer: Results from a randomized, open-label, phase 3 trial (ARCHER 1050). PG - 176-185 LID - S0169-5002(21)00085-4 [pii] LID - 10.1016/j.lungcan.2021.02.025 [doi] AB - OBJECTIVES: To compare efficacy and safety of dacomitinib versus gefitinib as first-line therapy for EGFR mutation-positive advanced NSCLC in Asian patients enrolled in the ongoing ARCHER 1050 trial. MATERIALS AND METHODS: In this ongoing, randomized, open-label, phase 3 trial (NCT01774721), eligible patients with newly diagnosed advanced EGFR mutation-positive NSCLC were randomized (1:1) to receive oral dacomitinib 45 mg/day or oral gefitinib 250 mg/day. Randomization, by a central computer system, was stratified by race and EGFR mutation type (exon 19 deletion mutation/exon 21 L858R substitution mutation). The primary endpoint was PFS by blinded independent review. RESULTS: Of 346 Asian patients, 170 were randomized to dacomitinib and 176 to gefitinib. The hazard ratio (HR) for PFS with dacomitinib versus gefitinib was 0.509 (95 % confidence interval [CI]: 0.391-0.662; 1-sided p < 0.0001; median 16.5 months [95 % CI: 12.9-18.4] vs. 9.3 months [95 % CI: 9.2-11.0]). HR for OS with dacomitinib versus gefitinib was 0.759 (95 % CI: 0.578-0.996; median 37.7 months [95 % CI: 30.2-44.7] vs. 29.1 months [95 % CI: 25.6-36.0]). The OS benefit was still maintained in those patients who had a stepwise dose reduction of dacomitinib (to 30 and 15 mg/day). The most common adverse events (AEs) were diarrhea (154 [90.6 %] patients), paronychia (110 [64.7 %]), dermatitis acneiform (96 [56.5 %]), and stomatitis (87 [51.2 %]) with dacomitinib, and diarrhea (100 [56.8 %]), alanine aminotransferase increased (81 [46.0 %]), and aspartate aminotransferase increased (75 [42.6 %]) with gefitinib. Treatment-related serious AEs were reported in 16 (9.4 %) and 8 (4.5 %) patients treated with dacomitinib and gefitinib, respectively. CONCLUSION: First-line dacomitinib was associated with significant prolongation of PFS and improved OS compared with gefitinib in Asian patients with EGFR mutation-positive advanced NSCLC. The AE profiles of dacomitinib and gefitinib in Asian patients were consistent with the overall ARCHER 1050 population. CI - Copyright (c) 2021 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Cheng, Ying AU - Cheng Y AD - Jilin Provincial Cancer Hospital, Changchun, China. FAU - Mok, Tony S AU - Mok TS AD - State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong, China. FAU - Zhou, Xiangdong AU - Zhou X AD - First Affiliated Hospital of Third Military Medical University, Chongqing, China. FAU - Lu, Shun AU - Lu S AD - Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. FAU - Zhou, Qing AU - Zhou Q AD - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China. FAU - Zhou, Jianying AU - Zhou J AD - First Affiliated Hospital of Zhejiang University, Hangzhou, China. FAU - Du, Yingying AU - Du Y AD - The First Affiliated Hospital of Anhui Medical University, Hefei, China. FAU - Yu, Ping AU - Yu P AD - Sichuan Cancer Hospital, Chengdu, China. FAU - Liu, Xiaoqing AU - Liu X AD - Department of Lung Cancer, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. FAU - Hu, Chengping AU - Hu C AD - Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China. FAU - Lu, You AU - Lu Y AD - Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Zhang, Yiping AU - Zhang Y AD - Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China. FAU - Lee, Ki Hyeong AU - Lee KH AD - Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, South Korea. FAU - Nakagawa, Kazuhiko AU - Nakagawa K AD - Kindai University Hospital, Osaka, Japan. FAU - Linke, Rolf AU - Linke R AD - SFJ Pharmaceuticals Inc., Pleasanton, CA, USA. FAU - Wong, Chew Hooi AU - Wong CH AD - Pfizer Pte. Ltd., Singapore. FAU - Tang, Yiyun AU - Tang Y AD - Pfizer Oncology, La Jolla, CA, USA. FAU - Zhu, Fanfan AU - Zhu F AD - Pfizer Investment Co., Ltd., Shanghai, China. FAU - Wilner, Keith D AU - Wilner KD AD - Pfizer Inc., San Diego, CA, USA. FAU - Wu, Yi-Long AU - Wu YL AD - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China. Electronic address: syylwu@live.cn. LA - eng SI - ClinicalTrials.gov/NCT01774721 PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210223 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Protein Kinase Inhibitors) RN - 0 (Quinazolinones) RN - 5092U85G58 (dacomitinib) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics MH - Disease-Free Survival MH - ErbB Receptors/genetics MH - Humans MH - *Lung Neoplasms/drug therapy/genetics MH - Mutation MH - Protein Kinase Inhibitors/adverse effects MH - Quinazolinones OTO - NOTNLM OT - Asian OT - Dacomitinib OT - Epidermal growth factor receptor OT - Non-small cell lung cancer OT - Tyrosine kinase inhibitor EDAT- 2021/03/16 06:00 MHDA- 2021/06/22 06:00 CRDT- 2021/03/15 20:12 PHST- 2020/11/16 00:00 [received] PHST- 2021/02/10 00:00 [revised] PHST- 2021/02/18 00:00 [accepted] PHST- 2021/03/16 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2021/03/15 20:12 [entrez] AID - S0169-5002(21)00085-4 [pii] AID - 10.1016/j.lungcan.2021.02.025 [doi] PST - ppublish SO - Lung Cancer. 2021 Apr;154:176-185. doi: 10.1016/j.lungcan.2021.02.025. Epub 2021 Feb 23.