MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer
MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer
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DOI：
10.1200/jco.2017.75.6155
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发表时间：
2017-11-10
影响因子：
45.3
通讯作者：
Di Leo, Angelo
中科院分区：
文献类型：
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作者：
Goetz, Matthew P.;Toi, Masakazu;Di Leo, Angelo
Abemaciclib是一种细胞周期蛋白依赖性激酶4和6抑制剂，在既往接受过内分泌治疗的激素受体（HR）阳性、人表皮生长因子受体2（HER 2）阴性的晚期乳腺癌患者中，单药治疗和与氟维司群联合治疗均显示出疗效。在493例既往未接受过晚期全身治疗的HR阳性、HER 2阴性晚期乳腺癌绝经后女性中开展的abemaciclib或安慰剂加非甾体类芳香酶抑制剂的随机III期研究。患者接受abemaciclib或安慰剂（150 mg，每日两次，连续给药方案）加1 mg阿那曲唑或2.5 mg来曲唑，每日一次。主要目的是评估者评估的无进展生存期。次要目的包括疗效评价和安全性。计划在189起事件后进行中期分析。结果abemaciclib组的中位无进展生存期显着延长（风险比，0.54; 95%CI，0.41至0.72; P = .000021;中位数：abemaciclib组未达到，安慰剂组为14.7个月）。在有可测量疾病的患者中，abemaciclib组的客观缓解率为59%，安慰剂组为44%（P = 0.004）。在abemaciclib组中，腹泻是最常见的不良反应（81.3%），但主要为1级（44.6%）。比较abemaciclib和安慰剂，最常见的3级或4级不良事件是中性粒细胞减少症（21.1%对1.2%），腹泻（9.5%对1.2%）和白细胞减少症（7.6%v0.6%）。结论Abemaciclib联合非甾体芳香酶抑制剂作为初始治疗是有效的，显著改善HR阳性、HER 2阴性晚期乳腺癌女性患者的无进展生存期和客观缓解率，并显示出可耐受的安全性特征。(C)2017年美国临床肿瘤学会
PurposeAbemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy.MethodsMONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole, daily. The primary objective was investigator-assessed progression-free survival. Secondary objectives included response evaluation and safety. A planned interim analysis occurred after 189 events.ResultsMedian progression-free survival was significantly prolonged in the abemaciclib arm (hazard ratio, 0.54; 95% CI, 0.41 to 0.72; P = .000021; median: not reached in the abemaciclib arm, 14.7 months in the placebo arm). In patients with measurable disease, the objective response rate was 59% in the abemaciclib arm and 44% in the placebo arm (P = .004). In the abemaciclib arm, diarrhea was the most frequent adverse effect (81.3%) but was mainly grade 1 (44.6%). Comparing abemaciclib and placebo, the most frequent grade 3 or 4 adverse events were neutropenia (21.1% v 1.2%), diarrhea (9.5% v 1.2%), and leukopenia (7.6% v 0.6%).ConclusionAbemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer. (C) 2017 by American Society of Clinical Oncology