دورية أكاديمية
Efficacy and Safety of Limertinib (ASK120067) in Patients With Locally Advanced or Metastatic EGFR Thr790Met-Mutated NSCLC: A Multicenter, Single-Arm, Phase 2b Study.
| العنوان: | Efficacy and Safety of Limertinib (ASK120067) in Patients With Locally Advanced or Metastatic EGFR Thr790Met-Mutated NSCLC: A Multicenter, Single-Arm, Phase 2b Study. |
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| المؤلفون: | Shi Y; Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People's Republic of China. Electronic address: syuankai@cicams.ac.cn., Li B; Integrated Department, Beijing Chest Hospital, Capital Medical University, Beijing, People's Republic of China., Wu L; Department of Medical Oncology-Chest (2), Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China., Pan Y; Cancer Chemotherapy Department, Anhui Provincial Hospital, The First Affiliated Hospital of USTC, Hefei, People's Republic of China., Pan Z; Department of Respiratory Diseases, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People's Republic of China., Liu Y; Department of Medical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China., Fan Y; Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China., Ji Y; Medical Oncology Ward 2, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, People's Republic of China., Fang J; Department of Thoracic Oncology II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/ Beijing), Peking University Cancer Hospital and Institute, Beijing, People's Republic of China., Shi Q; Oncology Department, Fuzhou Pulmonary Hospital of Fujian, Fuzhou, People's Republic of China., Shi J; Department II of Medical Oncology, Linyi Cancer Hospital, Linyi, People's Republic of China., Gao H; Pulmonary Oncology Department, Fifth Medical Center of Chinese PLA General Hospital, Beijing, People's Republic of China., Hu Y; Department of Thoracic Oncology, Hubei Cancer Hospital, The Affiliated Cancer Hospital of Tongji School of Medicine, Huazhong University of Science and Technology, Wuhan, People's Republic of China., Wang X; Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou, People's Republic of China., He Z; Department of Thoracic Oncology, Fujian Cancer Hospital, The Affiliated Cancer Hospital of Fujian Medical University, Fuzhou, People's Republic of China., Ma R; Department II of Chest Physicians, Liaoning Cancer Hospital & Institute, Shenyang, People's Republic of China., Zhang Y; Department I of Respiratory Medicine, Nanjing Chest Hospital, Medical School of Southeast University, Nanjing, People's Republic of China., Jiang D; Medical of Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China., Bai Y; Oncology Hematology Department, China-Japan Union Hospital of Jilin University, Changchun, People's Republic of China., Zhang Y; Thoracic Surgery Department, Xuanwu Hospital, Capital Medical University, Beijing, People's Republic of China., Huang L; Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical College, Bengbu, People's Republic of China., Zhou T; Oncology Department, Changzhou Tumor Hospital, Changzhou, People's Republic of China., Liu H; Department of Thoracic Medical Oncology, First People's Hospital of Chenzhou City, Chenzhou, People's Republic of China., Wang D; Department of Medical Oncology, Harrison International Peace Hospital, Hengshui, People's Republic of China., Wen Q; Oncology Department, The Affiliated Hospital of Southwest Medical University, Luzhou, People's Republic of China., Chen G; Department of Medical Oncology, Tumor Hospital of Harbin Medical University, Harbin, People's Republic of China., Zang A; Medicine Oncology, Affiliated Hospital of Hebei University, Baoding, People's Republic of China., Wang X; Department of Medical Oncology, Qilu Hospital of Shandong University, Jinan, People's Republic of China., Zhang X; Department of Respiratory and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, People's Republic of China., Hu J; Oncology Department, Yueyang Central hospital, Yueyang, People's Republic of China., Yang R; Internal Second Department, Yunnan Cancer hospital, Kunming, People's Republic of China., Zhang G; Department 1 of Pulmonary & Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China., Gu K; Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China., Wang L; Department of Medical Oncology, Hainan General Hospital, Haikou, People's Republic of China., Wang Q; Department of Medical Oncology, Henan Cancer Hospital, Zhengzhou, People's Republic of China., Wei Z; Pulmonary and Critical Care Medicine Department, The People's Hospital of Nanchuan, Chongqing, People's Republic of China., Li Z; Department of Oncology, 3201 Hospital, Hanzhong, People's Republic of China., Lu H; Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China., Zhang H; Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China., Chen H; Jiangsu Aosaikang Pharmaceutical Co. Ltd., Nanjing, People's Republic of China., Song T; Jiangsu Aosaikang Pharmaceutical Co. Ltd., Nanjing, People's Republic of China. |
| المصدر: | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [J Thorac Oncol] 2022 Oct; Vol. 17 (10), pp. 1205-1215. Date of Electronic Publication: 2022 Jun 02. |
| نوع المنشور: | Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 101274235 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1556-1380 (Electronic) Linking ISSN: 15560864 NLM ISO Abbreviation: J Thorac Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2016- : New York, NY : Elsevier Original Publication: Hagerstown, MD : Lippincott Williams & Wilkins, c2006- |
| مواضيع طبية MeSH: | Antineoplastic Agents*/adverse effects , Carcinoma, Non-Small-Cell Lung*/drug therapy , Carcinoma, Non-Small-Cell Lung*/genetics , Carcinoma, Non-Small-Cell Lung*/pathology , Exanthema* , Lung Neoplasms*/drug therapy , Lung Neoplasms*/genetics , Lung Neoplasms*/pathology, Acrylamides ; Aniline Compounds/therapeutic use ; Diarrhea/chemically induced ; ErbB Receptors ; Humans ; Mutation ; Protein Kinase Inhibitors/adverse effects |
| مستخلص: | Introduction: Limertinib (ASK120067) is a newly developed third-generation EGFR tyrosine kinase inhibitor targeting both sensitizing EGFR and EGFR Thr790Met (T790M) mutations. This study aimed to evaluate the efficacy and safety of limertinib in patients with locally advanced or metastatic EGFR T790M-mutated NSCLC. Methods: This is a single-arm, open-label, phase 2b study conducted at 62 hospitals across the People's Republic of China. Patients with locally advanced or metastatic NSCLC with centrally confirmed EGFR T790M mutations in tumor tissue or blood plasma who progressed after first- or second-generation EGFR tyrosine kinase inhibitors or with primary EGFR T790M mutations were enrolled. Patients received limertinib 160 mg orally twice daily until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) assessed by independent review committee per the Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included disease control rate, progression-free survival (PFS), duration of response (DoR), overall survival, and safety. Safety was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Results: From July 16, 2019, to March 10, 2021, a total of 301 patients were enrolled and started the treatment of limertinib. All patients entered the full analysis set and safety set. By the data cutoff date on September 9, 2021, 76 (25.2%) remained on treatment. The median follow-up time was 10.4 months (range: 0.3-26.3). On the basis of full analysis set, the independent review committee-assessed ORR was 68.8% (95% confidence interval [CI]: 63.2%-74.0%) and disease control rate was 92.4% (95% CI: 88.8%-95.1%). The median PFS was 11.0 months (95% CI: 9.7-12.4), median DoR was 11.1 months (95% CI: 9.6-13.8), and median OS was not reached (95% CI 19.7 months-not evaluable). Objective responses were achieved across all prespecified subgroups. For 99 patients (32.9%) with central nervous system (CNS) metastases, the ORR was 64.6% (95% CI: 54.4%-74.0%), median PFS was 9.7 months (95% CI: 5.9-11.6), and median DoR was 9.6 months (95% CI: 8.1-15.2). For 41 patients who had assessable CNS lesion, the confirmed CNS-ORR was 56.1% (95% CI: 39.7%-71.5%) and median CNS-PFS was 10.6 months (95% CI: 5.6-not evaluable). In safety set, 289 patients (96.0%) experienced at least one treatment-related adverse event (TRAE), with the most common being diarrhea (81.7%), anemia (32.6%), rash (29.9%), and anorexia (28.2%). Grade ≥3 TRAEs occurred in 104 patients (34.6%), with the most common including diarrhea (13.0%), hypokalemia (4.3%), anemia (4.0%), and rash (3.3%). TRAEs leading to dose interruption and dose discontinuation occurred in 24.6% and 2% of patients, respectively. No TRAE leading to death occurred. Conclusions: Limertinib (ASK120067) was found to have promising efficacy and an acceptable safety profile for the treatment of patients with locally advanced or metastatic EGFR T790M-mutated NSCLC. Clinical Trial Information: NCT03502850. (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: ASK120067; EGFR T790M mutation; Limertinib; Third-generation EGFR-TKI |
| سلسلة جزيئية: | ClinicalTrials.gov NCT03502850 |
| المشرفين على المادة: | 0 (Acrylamides) 0 (Aniline Compounds) 0 (Antineoplastic Agents) 0 (Protein Kinase Inhibitors) EC 2.7.10.1 (EGFR protein, human) EC 2.7.10.1 (ErbB Receptors) |
| تواريخ الأحداث: | Date Created: 20220606 Date Completed: 20221005 Latest Revision: 20221103 |
| رمز التحديث: | 20240513 |
| DOI: | 10.1016/j.jtho.2022.05.011 |
| PMID: | 35659581 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1556-1380 |
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| DOI: | 10.1016/j.jtho.2022.05.011 |