辅助阿贝西利联合内分泌治疗高危早期乳腺癌： monarchE 研究的更新疗效和 Ki-67 分析。

Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study.

机构信息

Breast Center, Department of OB & GYN and CCC Munich, LMU University Hospital, Munich, Germany.

University of Pittsburgh/UPMC, NSABP Foundation, Pittsburgh, USA.

出版信息

Ann Oncol. 2021 Dec;32(12):1571-1581. doi: 10.1016/j.annonc.2021.09.015. Epub 2021 Oct 14.

DOI:10.1016/j.annonc.2021.09.015

PMID:34656740

Abstract

BACKGROUND

Adjuvant abemaciclib combined with endocrine therapy (ET) previously demonstrated clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer at the second interim analysis, however follow-up was limited. Here, we present results of the prespecified primary outcome analysis and an additional follow-up analysis.

PATIENTS AND METHODS

This global, phase III, open-label trial randomized (1 : 1) 5637 patients to adjuvant ET for ≥5 years ± abemaciclib for 2 years. Cohort 1 enrolled patients with ≥4 positive axillary lymph nodes (ALNs), or 1-3 positive ALNs and either grade 3 disease or tumor ≥5 cm. Cohort 2 enrolled patients with 1-3 positive ALNs and centrally determined high Ki-67 index (≥20%). The primary endpoint was IDFS in the intent-to-treat population (cohorts 1 and 2). Secondary endpoints were IDFS in patients with high Ki-67, DRFS, overall survival, and safety.

RESULTS

At the primary outcome analysis, with 19 months median follow-up time, abemaciclib + ET resulted in a 29% reduction in the risk of developing an IDFS event [hazard ratio (HR) = 0.71, 95% confidence interval (CI) 0.58-0.87; nominal P = 0.0009]. At the additional follow-up analysis, with 27 months median follow-up and 90% of patients off treatment, IDFS (HR = 0.70, 95% CI 0.59-0.82; nominal P < 0.0001) and DRFS (HR = 0.69, 95% CI 0.57-0.83; nominal P < 0.0001) benefit was maintained. The absolute improvements in 3-year IDFS and DRFS rates were 5.4% and 4.2%, respectively. Whereas Ki-67 index was prognostic, abemaciclib benefit was consistent regardless of Ki-67 index. Safety data were consistent with the known abemaciclib risk profile.

CONCLUSION

Abemaciclib + ET significantly improved IDFS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer, with an acceptable safety profile. Ki-67 index was prognostic, but abemaciclib benefit was observed regardless of Ki-67 index. Overall, the robust treatment benefit of abemaciclib extended beyond the 2-year treatment period.

摘要

背景

在第二次中期分析时，阿贝西利联合内分泌治疗（ET）在激素受体阳性、人表皮生长因子受体 2 阴性、淋巴结阳性、高危早期乳腺癌患者中，显著改善了浸润性无病生存期（IDFS）和远处无复发生存期（DRFS），达到了临床有意义的改善，然而随访时间有限。在此，我们报告预设的主要结局分析和另外的随访分析结果。

患者和方法

这是一项全球性、III 期、开放性标签试验，将 5637 名患者随机（1：1）分为接受辅助 ET 治疗至少 5 年±阿贝西利治疗 2 年的两组。队列 1纳入了腋窝淋巴结阳性（ALN）≥4 个，或 1-3 个 ALN 阳性且疾病分级为 3 级或肿瘤直径≥5cm 的患者。队列 2纳入了 ALN 阳性 1-3 个且中心测定的 Ki-67 指数≥20%的患者。主要终点是意向治疗人群（队列 1 和 2）的 IDFS。次要终点包括 Ki-67 高的患者的 IDFS、DRFS、总生存期和安全性。

结果

在主要结局分析中，中位随访时间为 19 个月，阿贝西利+ET 使 IDFS 事件的风险降低了 29%（风险比[HR] = 0.71，95%置信区间[CI] 0.58-0.87；名义 P = 0.0009）。在另外的随访分析中，中位随访时间为 27 个月，90%的患者已停药，IDFS（HR = 0.70，95%CI 0.59-0.82；名义 P < 0.0001）和 DRFS（HR = 0.69，95%CI 0.57-0.83；名义 P < 0.0001）获益得以维持。3 年 IDFS 和 DRFS 率的绝对改善分别为 5.4%和 4.2%。虽然 Ki-67 指数是预后因素，但阿贝西利的获益与 Ki-67 指数无关。安全性数据与已知的阿贝西利风险特征一致。