Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE).
Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE).
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DOI：
10.1200/jco.20.02514
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发表时间：
2020-12-01
期刊：
影响因子：
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通讯作者：
monarchE Committee Members and Investigators
中科院分区：
文献类型：
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作者：
Johnston SRD;Harbeck N;Hegg R;Toi M;Martin M;Shao ZM;Zhang QY;Martinez Rodriguez JL;Campone M;Hamilton E;Sohn J;Guarneri V;Okada M;Boyle F;Neven P;Cortés J;Huober J;Wardley A;Tolaney SM;Cicin I;Smith IC;Frenzel M;Headley D;Wei R;San Antonio B;Hulstijn M;Cox J;O'Shaughnessy J;Rastogi P;monarchE Committee Members and Investigators
许多HR+、HER 2 −早期乳腺癌（EBC）患者在目前可用的标准疗法下不会复发或远处复发。然而，高达30%的具有高风险临床和/或病理特征的患者可能会经历远处复发，许多在最初几年内。需要更好的上级治疗方案来预防这组患者的早期复发和转移。Abemaciclib是一种口服、连续给药的CDK 4/6抑制剂，已获批用于治疗HR+、HER 2 −晚期乳腺癌（ABC）。abemaciclib在ABC中的有效性和安全性支持在辅助治疗环境中的评价。这项开放标签、III期研究纳入了HR+、HER 2 −、高风险EBC患者，这些患者接受了手术和放疗（如有指征）和/或辅助/新辅助化疗。具有4个或更多阳性淋巴结或1 - 3个淋巴结且肿瘤大小≥ 5 cm、组织学分级3级或中心Ki-67 ≥ 20%的患者符合资格，并随机（1：1）分配至标准辅助内分泌治疗（ET）联合或不联合abemaciclib（150 mg，每日2次，持续2年）。主要终点是无侵袭性疾病生存期（IDFS），次要终点包括无远处复发生存期、总生存期和安全性。在预先计划的疗效中期分析中，在5，637例随机分配的患者中，在意向治疗人群中观察到323起IDFS事件。Abemaciclib + ET显示出上级IDFS优于ET单药治疗（P = 0.01;风险比，0.75; 95% CI，0.60 - 0.93），2年IDFS率分别为92.2%和88.7%。安全性数据与abemaciclib的已知安全性特征一致。Abemaciclib与ET联合使用是第一种CDK 4/6抑制剂，在早期复发高风险的HR+、HER 2 −淋巴结阳性EBC患者中显示出IDFS的显著改善。
Many patients with HR+, HER2− early breast cancer (EBC) will not experience recurrence or have distant recurrence with currently available standard therapies. However, up to 30% of patients with high-risk clinical and/or pathologic features may experience distant recurrence, many in the first few years. Superior treatment options are needed to prevent early recurrence and development of metastases for this group of patients. Abemaciclib is an oral, continuously dosed, CDK4/6 inhibitor approved for HR+, HER2− advanced breast cancer (ABC). Efficacy and safety of abemaciclib in ABC supported evaluation in the adjuvant setting. This open-label, phase III study included patients with HR+, HER2−, high-risk EBC, who had surgery and, as indicated, radiotherapy and/or adjuvant/neoadjuvant chemotherapy. Patients with four or more positive nodes, or one to three nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%, were eligible and randomly assigned (1:1) to standard-of-care adjuvant endocrine therapy (ET) with or without abemaciclib (150 mg twice daily for 2 years). The primary end point was invasive disease-free survival (IDFS), and secondary end points included distant relapse–free survival, overall survival, and safety. At a preplanned efficacy interim analysis, among 5,637 randomly assigned patients, 323 IDFS events were observed in the intent-to-treat population. Abemaciclib plus ET demonstrated superior IDFS versus ET alone (P = .01; hazard ratio, 0.75; 95% CI, 0.60 to 0.93), with 2-year IDFS rates of 92.2% versus 88.7%, respectively. Safety data were consistent with the known safety profile of abemaciclib. Abemaciclib when combined with ET is the first CDK4/6 inhibitor to demonstrate a significant improvement in IDFS in patients with HR+, HER2− node-positive EBC at high risk of early recurrence.