期刊
JOURNAL OF THORACIC ONCOLOGY
卷 14, 期 10, 页码 1853-1859出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jtho.2019.06.027
关键词
Lung cancer; Targeted therapy; Squamous NSCLC; Cell cycle gene alteration; Cyclin-dependent kinase; Master protocol
资金
- National Institutes of Health/National Cancer Institute [CA180888, CA180819, CA180820, CA180821, CA180868, CA189821, CA189812, CA180801, CA189830, CA189872, CA180846, CA189873, CA 189822, CA 189809, CA180828, CA180834, CA190002, CA189954, CA180818, CA180826, CA46368, CA46282, CA11083]
- Amgen through the Foundation for the National Institutes of Health
- AstraZeneca through the Foundation for the National Institutes of Health
- Bristol-Myers Squibb Company through the Foundation for the National Institutes of Health
- Genentech through the Foundation for the National Institutes of Health
- Pfizer through the Foundation for the National Institutes of Health
- Friends of Cancer Research
Objective: Lung-MAP (SWOG S1400) is a master platform trial assessing targeted therapies in squamous NSCLC. The objective of study C (S1400C) was to evaluate the response rate to palbociclib, a cyclin-dependent kinase 4 and cyclin-dependent kinase 6 inhibitor, in patients with cell cycle gene abnormalities. Methods: Patients with squamous NSCLC, a performance status of 0 to 2, and normal organ function who had progressed after at least one prior platinum-based chemotherapy with cyclin-dependent kinase 4 gene (CDK4) or cyclin D1 gene (CCND1), cyclin D2 gene (CCND2), or cyclin D3 gene (CCND3) amplifications on tumor specimens were eligible. The study was originally designed as a phase II/III trial comparing palbociclib with docetaxel, but it was modified to a single-arm phase II trial with the primary end point of response when immunotherapy was approved. If two or fewer responses were seen in the first 20 patients, then the study would cease enrollment. Results: A total of 88 patients (9% of patients screened) were assigned to S1400C, and 53 patients enrolled (including 17 to receive docetaxel). One patient who had been registered to receive docetaxel was re-registered to receive palbociclib after progression while taking docetaxel. The frequencies of cell cycle gene alterations in the eligible patients taking palbociclib (n = 32) were as follows: CCND1, 81% (n = 26); CCND2, 9% (n = 3); CCND3, 6%(n = 2); and CDK4, 3% (n = 1). In all, 32 eligible patients received palbociclib. There were two partial responses (response rate 6% [ 95% confidence interval (CI): 0%-15%]), both with CCND1 amplification. Twelve patients had stable disease (38% [ 95% CI: 21%-54%]). The median progression-free survival was 1.7 months (95% CI: 1.6-2.9 months) and the median overall survival was 7.1 months (95% CI: 4.2-12.5). Conclusion: Palbociclib as monotherapy failed to demonstrate the prespecified criteria for advancement to phase III testing. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据