中国医学科学院肿瘤医院徐兵河等研究人员完成dalpiciclib或安慰剂加氟维司群治疗激素受体阳性和HER2阴性晚期乳腺癌的临床试验。2021年11月4日，国际知名学术期刊《自然—医学》在线发表了这一成果。

研究人员报告了DAWNA-1（NCT03927456）的中期结果，这是一项双盲、随机、3期试验，采用dalpiciclib（一种新的细胞周期蛋白依赖性激酶4和6抑制剂）加氟维司群治疗激素受体阳性、HER2阴性、内分泌治疗后出现疾病进展的晚期乳腺癌（ABC）。共有361名患者以2:1的比例随机接受dalpiciclib加氟维司群或安慰剂加氟维司群。

该研究达到了主要终点，显示dalpiciclib加氟维司群与安慰剂加氟维司群相比，调查者评估的无进展生存期明显延长（中位数=15.7，95%置信区间（CI）=11.1-未达到与7.2，95%CI=5.6-9.2个月；风险比=0.42，95%CI=0.31-0.58；单侧P<0.0001（边界为P≤0.008）。dalpiciclib加氟维司群最常见的3级或4级不良事件是中性粒细胞减少症（84.2%）和白细胞减少症（62.1%）。dalpiciclib加氟维司群的严重不良事件发生率为5.8%，而安慰剂加氟维司群为6.7%。这些研究结果支持dalpiciclib加氟维司群作为激素受体阳性、HER2阴性ABC的新治疗方案。

据介绍，阻断细胞周期蛋白依赖性激酶4和6通路已被证明对治疗激素受体阳性的ABC有效。

附：英文原文

Title: Dalpiciclib or placebo plus fulvestrant in hormone receptor-positive and HER2-negative advanced breast cancer: a randomized, phase 3 trial

Author: Xu, Binghe, Zhang, Qingyuan, Zhang, Pin, Hu, Xichun, Li, Wei, Tong, Zhongsheng, Sun, Tao, Teng, Yuee, Wu, Xinhong, Ouyang, Quchang, Yan, Xi, Cheng, Jing, Liu, Qiang, Feng, Jifeng, Wang, Xiaojia, Yin, Yongmei, Shi, Yanxia, Pan, Yueyin, Wang, Yongsheng, Xie, Weimin, Yan, Min, Liu, Yunjiang, Yan, Ping, Wu, Fei, Zhu, Xiaoyu, Zou, Jianjun

Issue&Volume: 2021-11-04

Abstract: Blockade of the cyclin-dependent kinase 4 and 6 pathway has been shown to be effective in the treatment of hormone receptor-positive advanced breast cancer (ABC). We report the interim results of DAWNA-1 (NCT03927456), a double-blind, randomized, phase 3 trial of dalpiciclib (a new cyclin-dependent kinase 4 and 6 inhibitor) plus fulvestrant in hormone receptor-positive, HER2-negative ABC with disease progression after endocrine therapy. A total of 361 patients were randomized 2:1 to receive dalpiciclib plus fulvestrant or placebo plus fulvestrant. The study met the primary end point, showing significantly prolonged investigator-assessed progression-free survival with dalpiciclib plus fulvestrant versus placebo plus fulvestrant (median=15.7, 95% confidence interval (CI)=11.1–not reached versus 7.2, 95% CI=5.6–9.2 months; hazard ratio=0.42, 95% CI=0.31–0.58; one-sided P<0.0001 (boundary was P≤0.008)). The most common grade 3 or 4 adverse events with dalpiciclib plus fulvestrant were neutropenia (84.2%) and leukopenia (62.1%). The incidence of serious adverse events was 5.8% with dalpiciclib plus fulvestrant versus 6.7% with placebo plus fulvestrant. Our findings support dalpiciclib plus fulvestrant as a new treatment option for pretreated hormone receptor-positive, HER2-negative ABC.

DOI: 10.1038/s41591-021-01562-9

Source: https://www.nature.com/articles/s41591-021-01562-9