Palbociclib 用于 CDK4 或 CDK6 扩增肿瘤患者的 2 期研究:NCI-MATCH ECOG-ACRIN 试验(EAY131)Z1C 子方案的结果

IF 10 1区 医学 Q1 ONCOLOGY
Mark H. O'Hara, Opeyemi Jegede, Mark A. Dickson, Angela M. DeMichele, Richard Piekarz, Robert J. Gray, Victoria Wang, Lisa M. McShane, Lawrence V. Rubinstein, David R. Patton, P. Mickey Williams, Stanley R. Hamilton, Adedayo Onitilo, James V. Tricoli, Barbara A. Conley, Carlos L. Arteaga, Lyndsay N. Harris, Peter J. O'Dwyer, Alice P. Chen, Keith T. Flaherty
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引用次数: 0

摘要

目的:CDK4和CDK6扩增是多种恶性肿瘤的特征之一,临床前证据表明,抑制CDK4/6是治疗这些肿瘤的一种可行策略。NCI-MATCH试验的Z1C子方案旨在评估CDK4/6抑制剂palbociclib在CDK4或CDK6扩增肿瘤中的疗效。患者和方法:患者均为实体瘤恶性肿瘤,至少接受过一次晚期疾病的全身治疗。CDK4或CDK6扩增≥7个拷贝的肿瘤被认为是扩增性肿瘤,符合分子研究条件。入组患者在28天周期的第1-21天每天接受帕博西尼125毫克的治疗。主要终点为ORR。研究结果43名患者加入了子方案Z1C,38名患者被认为符合条件、接受了治疗并纳入了分析;25名患者符合条件、接受了治疗并经中心证实CDK4或CDK6扩增,组成了ORR终点的主要分析队列。在 25 名主要队列患者中,1 名患者的最佳反应为 PR,4 名患者的最佳反应为 SD,16 名患者的最佳反应为 PD。4名患者因缺乏随访扫描而无法进行评估。在 38 名可评估的患者中,1 名患者有 PR,10 名患者有 SD,21 名患者的最佳反应为 PD。只有 CDK4 扩增的患者才出现部分应答和病情稳定。中位无进展生存期为 2.0 个月,中位总生存期为 8.8 个月。结论Palbociclib对组织学上不确定的CDK4或CDK6扩增肿瘤的活性有限,但中枢神经系统肿瘤可能值得未来研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Phase 2 Study of Palbociclib in Patients with Tumors with CDK4 or CDK6 Amplification: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Sub-protocol Z1C
Purpose: Amplification of CDK4 and CDK6 is a feature of a variety of malignancies, and preclinical evidence suggests inhibition of CDK4/6 is a plausible treatment strategy in these tumors. Subprotocol Z1C of the NCI-MATCH trial was designed to evaluate the CDK4/6 inhibitor palbociclib in CDK4- or CDK6-amplified tumors. Patients and Methods: Patients had a solid malignancy with progression on at least one systemic therapy for advanced disease. Tumors with ≥ 7 copies of CDK4 or CDK6 were considered amplified and molecularly eligible. Enrolled patients were treated with palbociclib 125 mg daily on days 1-21 of a 28-day cycle. The primary endpoint was ORR. Results: Forty-three patients were enrolled on subprotocol Z1C, and 38 patients were deemed eligible, treated, and included in analyses; 25 patients were eligible, treated, and centrally confirmed to have CDK4 or CDK6 amplification and comprised the primary analysis cohort for ORR endpoint. Among the 25 patients in the primary cohort, one patient had a PR, 4 patients had SD, and 16 patients had PD as best response. Four patients were not evaluable due to lack of follow-up scans. Among the 38 evaluable patients, one patient had a PR, 10 patients had SD, and 21 patients had PD as best response. Partial response and stable disease were only seen in patients with CDK4 amplification. Median progression-free survival was 2.0 months, and median overall survival was 8.8 months. Conclusions: Palbociclib showed limited activity in histology-agnostic CDK4- or CDK6-amplified tumors, though CNS tumors may be worthy of future investigation.
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来源期刊
Clinical Cancer Research
Clinical Cancer Research 医学-肿瘤学
CiteScore
20.10
自引率
1.70%
发文量
1207
审稿时长
2.1 months
期刊介绍: Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.
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