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前情提要：根据MONARCH 1、MONARCH 2研究，细胞周期蛋白依赖型激酶4和6抑制剂阿本昔布单药、阿本昔布＋氟维司群二线治疗既往内分泌疗法耐药的激素受体（HR）阳性且人类表皮生长因子受体2（HER2）阴性晚期乳腺癌女性有效。 2017年10月2日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表美国梅奥医院、日本京都大学、法国癌症研究所、法国莱昂贝拉中心、法国礼来、韩国延世大学癌症中心、韩国国家癌症中心、以色列希巴医疗中心、德国乌尔姆大学、中国台北长庚大学医学院、西班牙马德里康普顿斯大学独立日医院、西班牙礼来、加拿大达勒姆地区癌症中心、墨西哥卡米诺医疗集团、美国礼来、意大利普拉托医院的MONARCH 3研究报告，评估了非甾体芳香酶抑制剂±阿本昔布一线治疗HR阳性HER2阴性晚期乳腺癌患者的有效性和安全性。 该双盲随机III期研究（MONARCH 3）于2014年11月18日～2015年11月11日入组493例尚未接受未经全身治疗的HR阳性HER2阴性晚期乳腺癌绝经后女性，按2∶1随机接受阿本昔布（每天2次，每次150mg）或安慰剂＋非甾体芳香酶抑制剂（每天阿那曲唑1mg或来曲唑2.5mg）。主要终点为研究者评定的无进展生存，次要终点包括缓解率和安全性。计划于发生189例无进展生存事件之后进行中期分析。 结果发现，经过中位随访17.8个月、发生194例无进展生存事件（阿本昔布组32.9%、安慰剂组52.1%），阿本昔布组与安慰剂组相比：
阿本昔布组最常见的不良反应为腹泻，发生率81.3%，但是主要为1级（44.6%）。 阿本昔布组与安慰剂组相比，最常见的3～4级不良事件：
因此，对于HR阳性HER2阴性晚期乳腺癌患者，阿本昔布＋非甾体芳香酶抑制剂一线疗法有效，可以显著改善无进展生存和客观缓解率，不良反应可以耐受。 相关阅读 J Clin Oncol. 2017 Oct 2. [Epub ahead of print] MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. Mayo Clinic, Rochester, MN; Kyoto University, Kyoto, Japan; Institut de Cancerologie de l'Ouest, Angers Cedex; Centre Léon Bérard, Lyon; Eli Lilly, Paris, France; Yonsei Cancer Center, Seoul; National Cancer Center, Goyangsi, South Korea; Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; University of Ulm, Ulm, Germany; Chang Gung University Medical College, Taipei, Taiwan; Hospital Universitario 12 de Octubre; Eli Lilly, Madrid, Spain; Durham Regional Cancer Centre, Oshawa, Ontario, Canada; Grupo Médico CAMINO S.C., Mexico City, Mexico; Eli Lilly, Indianapolis, IN; Hospital of Prato, Prato, Italy. PURPOSE: 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. METHODS: 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. RESULTS: 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%). CONCLUSION: 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. PMID: 28968163 DOI: 10.1200/JCO.2017.75.6155
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