دورية أكاديمية
A Phase 1/2 Study of Lazertinib 240 mg in Patients With Advanced EGFR T790M-Positive NSCLC After Previous EGFR Tyrosine Kinase Inhibitors.
| العنوان: | A Phase 1/2 Study of Lazertinib 240 mg in Patients With Advanced EGFR T790M-Positive NSCLC After Previous EGFR Tyrosine Kinase Inhibitors. |
|---|---|
| المؤلفون: | Cho BC; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea., Han JY; Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea., Kim SW; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Lee KH; Division of Medical Oncology, Department of Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Republic of Korea., Cho EK; Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea., Lee YG; Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Kim DW; Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea., Kim JH; CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea., Lee GW; Division of Hematology and Oncology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, Republic of Korea., Lee JS; Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, Republic of Korea., Shim BY; Division of Medical Oncology, Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Republic of Korea., Kim JS; Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea., Chun SH; Division of Medical Oncology, Department of Internal Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea, Bucheon, Republic of Korea., Lee SS; Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea., Kim HR; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea., Hong MH; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea., Ahn JS; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Republic of Korea., Sun JM; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Republic of Korea., Lee Y; Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea., Lee DH; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Kang JA; Clinical Development Department, Yuhan Corporation, Seoul, Republic of Korea., Lee N; Clinical Development Department, Yuhan Corporation, Seoul, Republic of Korea., Kwon MJ; Clinical Development Department, Yuhan Corporation, Seoul, Republic of Korea., Espenschied C; Guardant Health, Inc., Redwood City, California., Yablonovitch A; Guardant Health, Inc., Redwood City, California., Ahn MJ; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Republic of Korea. Electronic address: silkahn@skku.edu. |
| المصدر: | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [J Thorac Oncol] 2022 Apr; Vol. 17 (4), pp. 558-567. Date of Electronic Publication: 2021 Dec 24. |
| نوع المنشور: | Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; 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: | Carcinoma, Non-Small-Cell Lung*/chemically induced , Carcinoma, Non-Small-Cell Lung*/drug therapy , Carcinoma, Non-Small-Cell Lung*/genetics , Lung Neoplasms*/chemically induced , Lung Neoplasms*/drug therapy , Lung Neoplasms*/genetics, Adult ; ErbB Receptors/genetics ; Humans ; Morpholines ; Mutation ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Pyrazoles ; Pyrimidines |
| مستخلص: | Introduction: This integrated analysis of a phase 1/2 study (NCT03046992) evaluated the efficacy and safety of lazertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), in patients with advanced EGFR T790M-positive NSCLC after previous EGFR TKI therapy. Methods: Adults with EGFR mutation-positive NSCLC that progressed after prior EGFR-directed TKIs received once daily oral lazertinib 240 mg continuously until disease progression. Prior TKIs to treat T790M-positive NSCLC were prohibited. Primary endpoints were safety and objective response rate (ORR). Secondary endpoints included progression-free survival, overall survival, and intracranial ORR. Results: A total of 78 patients received lazertinib 240 mg at 17 centers in South Korea. Among patients with T790M-positive tumors at baseline (N = 76), one (1.3%) had a complete response and 41 (53.9%) had partial responses, giving an ORR of 55.3% (95% confidence interval [CI]: 44.1-66.4). Median progression-free survival was 11.1 months (95% CI: 5.5-16.4). Median overall survival was not reached (median follow-up = 22.0 mo). In patients with measurable intracranial lesions (n = 7), one (14.3%) had a complete intracranial response and five (71.4%) had partial responses, giving an intracranial ORR of 85.7% (95% CI: 59.8%-100.0%). The most common treatment-emergent adverse events were rash (37.2%), pruritus (34.6%), and paresthesia (33.3%); most were mild to moderate in severity. Serious drug-related adverse events occurred in three patients (gastritis, pneumonia, pneumonitis). The major mechanism of resistance was EGFR T790M loss. Conclusions: Lazertinib 240 mg/d has a manageable safety profile with durable antitumor efficacy, including brain metastases, in patients with advanced T790M-positive NSCLC after previous EGFR TKI therapy. (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.) |
| التعليقات: | Comment in: J Thorac Oncol. 2022 Apr;17(4):481-486. (PMID: 35307103) Erratum in: J Thorac Oncol. 2022 Oct 22;:. (PMID: 36283923) |
| فهرسة مساهمة: | Keywords: EGFR T790M-positive non-small cell lung cancer (NSCLC); Epidermal growth factor receptor (EGFR); Lazertinib; Tyrosine kinase inhibitor (TKI) |
| سلسلة جزيئية: | ClinicalTrials.gov NCT03046992 |
| المشرفين على المادة: | 0 (Morpholines) 0 (Protein Kinase Inhibitors) 0 (Pyrazoles) 0 (Pyrimidines) 4A2Y23XK11 (lazertinib) EC 2.7.10.1 (EGFR protein, human) EC 2.7.10.1 (ErbB Receptors) |
| تواريخ الأحداث: | Date Created: 20211227 Date Completed: 20220429 Latest Revision: 20221025 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.jtho.2021.11.025 |
| PMID: | 34958928 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1556-1380 |
|---|---|
| DOI: | 10.1016/j.jtho.2021.11.025 |