Phase II Study of Palbociclib (PD-0332991) in CCND1, 2, or 3 Amplification: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1B.
Phase II Study of Palbociclib (PD-0332991) in CCND1, 2, or 3 Amplification: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1B.
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palbociclib（PD-0332991）在CCND1、2或3扩增中的II期研究：NCI匹配ECOG-ACRIN试验（EAY131）子协议Z1B的结果。
DOI：
10.1158/1078-0432.ccr-22-2150
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发表时间：
2023-04-14
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细胞周期蛋白D/CDK 4/6在控制G1到S检查点中至关重要。已知编码细胞周期蛋白D的基因CCND在多种实体瘤中扩增。Palbociclib是一种口服CDK 4/6抑制剂，已获批与内分泌治疗联合用于晚期乳腺癌。我们探索了Palbociclib在CCND 1、2或3扩增的非乳腺实体瘤患者中的疗效。肿瘤中含有CCND 1、2或3扩增和视网膜母细胞瘤蛋白表达的患者被分配至子方案Z1 B，并接受palbociclib 125 mg每日一次，持续21天，28天为一个周期。每两个周期评估一次肿瘤缓解。40例患者被分配至子方案Z1 B; 4例患者进行了鉴定CCND 1、2或3扩增的外部检测，但未在中心确认; 3例不合格，2例未接受治疗（1例未接受治疗的患者也不合格），本分析留下32例可评价患者。无部分缓解; 12例患者（37.5%）的最佳缓解为疾病稳定。研究期间有7例死亡，均发生在第1周期，可归因于疾病进展。中位无进展生存期为1.8个月。最常见的毒性是白细胞减少症（n = 21，55%）和中性粒细胞减少症（n = 19，50%）;中性粒细胞减少症是最常见的3/4级事件（n = 12，32%）。在该队列中，Palbociclib对治疗CCND 1、2或3扩增的非乳腺实体瘤无效。这些数据不支持palbociclib单药治疗CCND 1、2或3扩增肿瘤的进一步研究。
Cyclin D/CDK4/6 is critical in controlling the G1 to S checkpoint. CCND, the gene encoding cyclin D, is known to be amplified in a variety of solid tumors. Palbociclib is an oral CDK4/6 inhibitor, approved in advanced breast cancer in combination with endocrine therapy. We explored the efficacy of palbociclib in patients with nonbreast solid tumors containing an amplification in CCND1, 2, or 3. Patients with tumors containing a CCND1, 2, or 3 amplification and expression of the retinoblastoma protein were assigned to subprotocol Z1B and received palbociclib 125 mg once daily for 21 days of a 28-day cycle. Tumor response was assessed every two cycles. Forty patients were assigned to subprotocol Z1B; 4 patients had outside assays identifying the CCND1, 2, or 3 amplification and were not confirmed centrally; 3 were ineligible and 2 were not treated (1 untreated patient was also ineligible), leaving 32 evaluable patients for this analysis. There were no partial responses; 12 patients (37.5%) had stable disease as best response. There were seven deaths on study, all during cycle 1 and attributable to disease progression. Median progression-free survival was 1.8 months. The most common toxicities were leukopenia (n = 21, 55%) and neutropenia (n = 19, 50%); neutropenia was the most common grade 3/4 event (n = 12, 32%). Palbociclib was not effective at treating nonbreast solid tumors with a CCND1, 2, or 3 amplification in this cohort. These data do not support further investigation of single-agent palbociclib in tumors with CCND1, 2, or 3 amplification.