دورية أكاديمية
Lazertinib in EGFR-Variant Non-Small Cell Lung Cancer With CNS Failure to Prior EGFR Tyrosine Kinase Inhibitors: A Nonrandomized Controlled Trial.
| العنوان: | Lazertinib in EGFR-Variant Non-Small Cell Lung Cancer With CNS Failure to Prior EGFR Tyrosine Kinase Inhibitors: A Nonrandomized Controlled Trial. |
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| المؤلفون: | Hong MH; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea., Choi YJ; Division of Medical Oncology and Hematology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea., Ahn HK; Division of Medical Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea., Lim SM; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea., Keam B; Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea., Kim DW; Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea., Kim TM; Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea., Youk J; Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea., Kim YJ; Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea., Hwang S; Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea.; Department of Medicine, Physician-Scientist Program, Yonsei University College of Medicine, Seoul, Republic of Korea., Kim S; Department of Biomedical Systems Informatics and Graduate School of Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea., Kim JW; Division of Medical Oncology and Hematology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea., Kim HR; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea., Kang JH; Division of Medical Oncology, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. |
| المصدر: | JAMA oncology [JAMA Oncol] 2024 Aug 15. Date of Electronic Publication: 2024 Aug 15. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Medical Association Country of Publication: United States NLM ID: 101652861 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2374-2445 (Electronic) Linking ISSN: 23742437 NLM ISO Abbreviation: JAMA Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Chicago, Il : American Medical Association, [2015]- |
| مستخلص: | Importance: EGFR-variant non-small cell lung cancer (NSCLC) is associated with a high rate of central nervous system (CNS) metastases, even with treatment with first-generation or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Objective: To investigate CNS activity with lazertinib, a third-generation EGFR TKI. Design, Setting, and Participants: This multicenter single-arm, phase 2 nonrandomized controlled trial was conducted in South Korea and included patients with EGFR-variant NSCLC who had asymptomatic or mildly symptomatic brain metastases after unsuccessful treatment with first-generation or second-generation EGFR TKIs. Data were collected from June 2021 to April 2022, with a data cutoff date of December 15, 2022. Exposure: Lazertinib, 240 mg, once daily. Main Outcomes and Measures: The primary end point was intracranial objective response rate (iORR) in the evaluable population according to the Response Evaluation Criteria in Solid Tumours version 1.1 assessed by the investigators. Secondary end points included intracranial progression-free survival (iPFS) and iORR in patients with T790M-negative disease and isolated CNS progression as well as overall ORR, duration of response, intracranial duration of response, disease control rate, overall survival, cerebrospinal fluid penetration of lazertinib, and safety. Results: Among 40 included patients, 25 (63%) were women, and the median (range) age was 63 (29-85) years. A total of 38 patients were evaluable for tumor response, including 12 patients with leptomeningeal metastases. At data cutoff, the median (range) follow-up was 13.6 (2.9-17.7) months. The iORR for the evaluable population was 55% (21 of 38; 95% CI, 38.3-71.4); for patients with T790M-positive disease, 80% (4 of 5; 95% CI, 28.4-99.5); for patients with T790M-negative disease, 43% (9 of 21; 95% CI, 21.8-66.0); and for patients with T790M-unknown disease, 67% (8 of 12; 95% CI, 34.9-90.1). The median iPFS was 15.8 months (95% CI, 15.2-not reached) for the evaluable population, 15.2 months (95% CI, 4.2-not reached) for the T790M-positive subgroup, 15.4 months (95% CI, 7.9-not reached) for the T790M-negative subgroup, and 18.0 months (95% CI, 3.9-not reached) for the T790M-unknown subgroup. The cerebrospinal fluid penetration rate of lazertinib was 46.2% (95% CI, 10.0-49.6), providing further support for its mechanism of intracranial response. Most adverse events were grade 1 or 2. Conclusions and Relevance: In this study, lazertinib had substantial CNS activity, regardless of T790M status, against the progression of intracranial metastases with or without leptomeningeal metastases after unsuccessful treatment with first-generation or second-generation EGFR TKIs in patients with metastatic EGFR-variant NSCLC. These results suggest that using lazertinib instead of brain local treatment could be a potential strategy in patients with EGFR-variant NSCLC whose CNS metastases progressed after prior EGFR TKI treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT05326425. |
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| سلسلة جزيئية: | ClinicalTrials.gov NCT05326425 |
| تواريخ الأحداث: | Date Created: 20240815 Latest Revision: 20240818 |
| رمز التحديث: | 20240818 |
| مُعرف محوري في PubMed: | PMC11327907 |
| DOI: | 10.1001/jamaoncol.2024.2640 |
| PMID: | 39145962 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2374-2445 |
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| DOI: | 10.1001/jamaoncol.2024.2640 |