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.

中文翻译：

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


目的：CDK4 和 CDK6 的扩增是多种恶性肿瘤的一个特征，临床前证据表明抑制 CDK4/6 是这些肿瘤的一种合理的治疗策略。NCI-MATCH 试验的子方案 Z1C 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： 患者为实体恶性肿瘤，至少在一种晚期疾病全身治疗后进展。具有 ≥ 7 个 CDK4 或 CDK6 拷贝的肿瘤被认为扩增且分子合格。入组患者在 28 天周期的第 1-21 天每天服用 palbociclib 125 mg。主要终点是 ORR。结果： 43 例患者被纳入子方案 Z1C，其中 38 例患者被认为符合条件、接受治疗并纳入分析;25 例患者符合条件、接受治疗并集中确认有 CDK4 或 CDK6 扩增，构成了 ORR 终点的主要分析队列。在主要队列的 25 例患者中，1 例患者为 PR，4 例为 SD，16 例患者为 PD 为最佳反应。4 例患者由于缺乏随访扫描而无法评估。在 38 例可评估患者中，1 例患者为 PR，10 例患者为 SD，21 例患者为 PD 为最佳反应。部分缓解和疾病稳定仅见于 CDK4 扩增患者。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 在组织学无关的 CDK4 或 CDK6 扩增肿瘤中显示出有限的活性，尽管 CNS 肿瘤可能值得进一步研究。