MONARCH plus研究：阿贝西利联合内分泌治疗HR+/HER2-晚期乳腺癌女性患者的多中心随机III期研究
MONARCH plus: abemaciclib plus endocrine therapy in women with HR+/HER2- advanced breast cancer: the multinational randomized phase III study.
作者信息
Zhang Qing Yuan, Sun Tao, Yin Yong Mei, Li Hui Ping, Yan Min, Tong Zhong Sheng, Oppermann Christina P, Liu Yun Peng, Costa Romulo, Li Man, Cheng Ying, Ouyang Qu Chang, Chen Xi, Liao Ning, Wu Xin Hong, Wang Xiao Jia, Feng Ji Feng, Hegg Roberto, Kanakasetty G B, Coccia-Portugal Maria A, Han Ru Bing, Lu Yi, Chi Hai Dong, Jiang Ze Fei, Hu Xi Chun
机构信息
Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Department of Medical Oncology, Cancer Hospital of China Medical University/ Liaoning Cancer Hospital, Shenyang, China.
出版信息
Ther Adv Med Oncol. 2020 Oct 22;12:1758835920963925. doi: 10.1177/1758835920963925. eCollection 2020.
AIM
To compare the efficacy, safety, and tolerability of abemaciclib plus endocrine therapy (ET) ET alone in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) from China, Brazil, India, and South Africa.
METHODS
This randomized, double-blind, phase III study was conducted between 9 December 2016 and 29 March 2019. Postmenopausal women with HR-positive, HER2-negative ABC with no prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) received abemaciclib (150 mg twice daily) or placebo plus: anastrozole (1 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg per label) (cohort B). The primary endpoint was progression-free survival (PFS) in cohort A, analyzed using the stratified log-rank test. Secondary endpoints were PFS in cohort B (key secondary endpoint), objective response rate (ORR), and safety. This interim analysis was planned after 119 PFS events in cohort A.
RESULTS
In cohort A, 207 patients were randomly assigned to the abemaciclib arm and 99 to the placebo arm. Abemaciclib significantly improved PFS placebo (median: not reached 14.7 months; hazard ratio 0.499; 95% confidence intervals (CI) 0.346-0.719; = 0.0001). ORR was 65.9% in the abemaciclib arm and 36.1% in the placebo arm ( < 0.0001, measurable disease population). In cohort B, 104 patients were randomly assigned to the abemaciclib arm and 53 to the placebo arm. Abemaciclib significantly improved PFS placebo (median: 11.5 5.6 months; hazard ratio 0.376; 95% CI 0.240-0.588; < 0.0001). ORR was 50.0% in the abemaciclib arm and 10.5% in the placebo arm ( < 0.0001, measurable disease population). The most frequent grade ⩾3 adverse events in the abemaciclib arms were neutropenia, leukopenia, and anemia (both cohorts), and lymphocytopenia (cohort B).
CONCLUSION
The addition of abemaciclib to ET demonstrated significant and clinically meaningful improvement in PFS and ORR, without new safety signals observed in this population. ClinicalTrials.gov identifier: NCT02763566.
目的
比较阿贝西利联合内分泌治疗（ET）与单纯ET用于中国、巴西、印度和南非绝经后激素受体（HR）阳性、人表皮生长因子受体2（HER2）阴性晚期乳腺癌（ABC）患者的疗效、安全性和耐受性。
方法
本随机、双盲、III期研究于2016年12月9日至2019年3月29日进行。晚期未接受过全身治疗的HR阳性、HER2阴性ABC绝经后女性（队列A）或既往ET治疗进展的患者（队列B）接受阿贝西利（每日两次，每次150mg）或安慰剂加：阿那曲唑（每日1mg）或来曲唑（每日2.5mg）（队列A）或氟维司群（每瓶500mg）（队列B）。主要终点是队列A中的无进展生存期（PFS），采用分层对数秩检验进行分析。次要终点是队列B中的PFS（关键次要终点）、客观缓解率（ORR）和安全性。在队列A中发生119例PFS事件后进行了这项中期分析。
结果
在队列A中，207例患者被随机分配至阿贝西利组，99例被分配至安慰剂组。阿贝西利显著改善了PFS，优于安慰剂（中位数：未达到vs 14.7个月；风险比0.499；95%置信区间（CI）0.346 - 0.719；P = 0.0001）。阿贝西利组的ORR为65.9%，安慰剂组为36.1%（P < 0.0001，可测量疾病人群）。在队列B中，104例患者被随机分配至阿贝西利组，53例被分配至安慰剂组。阿贝西利显著改善了PFS，优于安慰剂（中位数：11.5 vs 5.6个月；风险比0.376；95% CI 0.240 - 0.588；P < 0.0001）。阿贝西利组的ORR为50.0%，安慰剂组为10.5%（P < 0.0001，可测量疾病人群）。阿贝西利组最常见的≥3级不良事件是中性粒细胞减少、白细胞减少和贫血（两个队列），以及淋巴细胞减少（队列B）。
结论
ET联合阿贝西利在PFS和ORR方面显示出显著且具有临床意义的改善，在该人群中未观察到新的安全信号。ClinicalTrials.gov标识符：NCT02763566。
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