针对晚期HR+HER2-乳腺癌的自加高剂量CDK4/6抑制剂:一期1b/2试验
Chang Gong1, Qun Lin1, Tao Qin1
1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
与高剂量palbociclib相结合的氧化对于在CDK4/6抑制剂上进展的激素受体阳性乳腺癌患者是安全有效的. 这种组合在治疗这种患者群体方面显示出有希望的疗效和耐受性毒性.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 临床试验 临床试验
背景情况:
- 对于管理激素受体阳性/人表皮生长因子受体2-阴性 (HR+/HER2-) 乳腺癌的未满足需求存在,这种癌症在循环素依赖激酶 (CDK) 4/6抑制剂 (CDK4/6i) 治疗后进展.
- 这项研究解决了这一患者亚组治疗策略缺乏明确性的问题.
研究的目的:
- 在先进的HR+/HER2-乳腺癌患者中,结合基 (HCQ) 和高剂量palbociclib的安全性和有效性进行评估,这些患者之前已经失败了CDK4/6抑制剂治疗.
- 为了确定该组合治疗的推第二阶段剂量 (RP2D).
主要方法:
- 一项1b/2期,单臂,开放性研究招募了29名HR+/HER2-乳腺癌后第一线palbociclib失败的患者.
- 主要终点是剂量限制性毒性 (DLT);次要终点包括客观反应率 (ORR) 和无进展生存期 (PFS).
- 患者接受了氧化 (HCQ;600毫克,bis in die [bid]) 以及升级剂量的palbociclib (100,150或200毫克,quaque die [qd]).
主要成果:
- 在1b阶段没有观察到剂量限制性毒性 (DLT). 推的第二阶段剂量 (RP2D) 确定为HCQ (600 mg, bid) 加上palbociclib (200 mg, qd).
- 该组合是可以容忍的,具有3级治疗出现的不良事件 (TEAE),包括中性质减退 (25.0%) 和白血减退 (25.0%).
- 客观反应率 (ORR) 为41.4% (12/29),六个月临床效益率 (CBR) 为90.0% (95% CI:68.3%-98.8%). 没有达到PFS中位数.
结论:
- 与高剂量的palbociclib联合氧化表明耐受性毒性和有前途的疗效在晚期HR+/HER2-乳腺癌患者中CDK4/6抑制剂失效后.
- 这种组合代表了先进HR+/HER2-乳腺癌患者的潜在治疗选择,这些患者在之前的CDK4/6抑制剂治疗中已经进展.
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