Novel CDK2/4/6 inhibitor culmerciclib (TQB3616) plus fulvestrant in previously treated, HR-positive, HER2-negative advanced breast cancer: a randomized, double-blind, phase 3 trial.
СтатьяРандомизированное исследованиеКлиническое исследование III фазыПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Yin Yongmei, Zhang Qingyuan, Sun Tao, Hao Chunfang, Wang Zhihong, Yang Jin, Wang Yongsheng, Shi Yanxia, Sun Jing, Ouyang Quchang, Su Haichuan, Wu Jinsheng, Gan Lu, Han Meng, Gao Liming, Wang Xiaojia, Zhao Bing, Li Hui, Zhao Jiuda, Yang Hongwei, Ning Fangling, Tian Fuguo, Zhang Juliang, Sun Hongmei, Niu Zhaofeng, Zong Hong, Zang Aimin, Wang Xinshuai, Qian Xinyu, Wu Shikai, Nie Jianyun, He Lijia, Cheng Ying, Hao Yanrong, Zhai Yi, Li Huiping, Wang Jingfen, Wei Shihong, Li Man, Liu Yunjiang, Guo Hongqiang, Hu Qun, Liu Lina, Han Xinghua, Luo Ruizhen, Ni Mingli, Tang Xianjun, Zhai Zhenhua, Ding Meiqian, Wang Haibo, Shen Peng, Wang Xian, Liu Lian, Chen Wenyan, Liu Gang, Cai Zhengwen, Jiang Zefei
Аннотация
CDK2 is a principal mediator of CDK4/6 resistance. Concurrent CDK2/4/6 blockade may be effective in treating HR-positive, HER2-negative advanced breast cancer (ABC). This randomized, double-blind, parallel-controlled, phase 3 trial (ClinicalTrials.gov, NCT05375461) assessed the efficacy of culmerciclib, a CDK2/4/6 inhibitor, plus fulvestrant in ABC. Patients with HR-positive, HER2-negative, locally recurrent or metastatic breast cancer were randomized (2:1) to receive culmerciclib plus fulvestrant or matching placebo plus fulvestrant. Between March 18, 2022 and March 3, 2023, 293 pretreated patients (median age 53.0 years; pre- or perimenopausal 42.3%; bone metastasis 65.2%) were randomized to assigned treatments. At this prespecified interim analysis, culmerciclib plus fulvestrant extended the median investigator-assessed progression-free survival (PFS) significantly, the primary endpoint, as compared with placebo plus fulvestrant (16.6 months, 95% CI 13.8 to not evaluable versus 7.5 months, 95% CI 5.3 to 11.0; hazard ratio 0.36, 95% CI 0.26-0.51; stratified log rank test P < 0.001). Consistent effects were observed across diverse subgroups of patients. At a median follow-up duration of 13.8 months, overall survival was immature. The investigators-assessed objective response rate was 40.2% (95% CI, 33.3-47.5) for culmerciclib compared to 12.1% (95% CI 6.4-20.2) for placebo (stratified Mantel-Haenszel χ2 test P < 0.001). Diarrhea (87.1%) and neutropenia (80.4%) were the most common toxicities with culmerciclib plus fulvestrant. In conclusion, this randomized clinical trial met its primary outcome. Culmerciclib plus fulvestrant is well tolerated and leads to a significant gain in PFS of pretreated HR-positive HER2-negative ABC patients.