Abemaciclib, 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.

MONARCH 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.

Median 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%).

Abemaciclib 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.

Abemaciclib，一种依赖细胞周期蛋白的激酶4和6抑制剂，在以前接受内分泌治疗的荷尔蒙受体（HR）阳性，人表皮生长因子受体2（HER2）阴性的晚期乳腺癌女性中证明了单一疗法的有效性和与氟维司群联用治疗。

MONARCH 3是abemaciclib或安慰剂加非类固醇芳香化酶抑制剂对HR阳性，HER2阴性的绝经后妇女进行的双盲，随机III期研究，该妇女在HR阳性，HER2阴性的晚期乳腺癌中未接受过全身性治疗。患者每天接受abemaciclib或安慰剂（150 mg连续两次，每天两次）加上1 mg阿那曲唑或2.5 mg来曲唑。主要目标是研究者评估的无进展生存期。次要目标包括响应评估和安全性。189次事件后进行了计划中的中期分析。

中度无进展生存期在abemaciclib组中显着延长（危险比，0.54； 95％CI，0.41至0.72；P = .000021；中位数：在abemaciclib组中未达到，在安慰剂组中为14.7个月）。在可测量疾病的患者中，阿贝西米lib组的客观缓解率为59％，安慰剂组为44％（P = .004）。在abemaciclib组中，腹泻是最常见的不良反应（81.3％），但主要是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％v 1.2％），腹泻（9.5％v 1.2％）和白细胞减少症（7.6％v 0.6％）。

Abemaciclib加非类固醇芳香化酶抑制剂可有效地作为初始治疗，显着提高无进展生存率和客观应答率，并证明HR阳性，HER2阴性的晚期乳腺癌妇女具有可耐受的安全性。