MONARCH 2 日本亚人群分析：一项 abemaciclib 联合氟维司群治疗激素受体阳性、人表皮生长因子受体 2 阴性乳腺癌的 III 期研究，该研究针对在内分泌治疗后进展的患者。
Japanese subpopulation analysis of MONARCH 2: phase 3 study of abemaciclib plus fulvestrant for treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer that progressed on endocrine therapy.
机构信息
Saitama Cancer Center, Saitama, Japan.
National Hospital Organization, Osaka National Hospital, Osaka, Japan.
出版信息
Breast Cancer. 2021 Sep;28(5):1038-1050. doi: 10.1007/s12282-021-01239-8. Epub 2021 Apr 1.
BACKGROUND
This was a Japanese subpopulation analysis of MONARCH 2, a double-blind, randomized, placebo-controlled, phase 3 study of abemaciclib plus fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC).
METHODS
Eligible women had progressed on (neo)adjuvant endocrine therapy (ET), ≤ 12 months from end of adjuvant ET, or on first-line ET for ABC, and had not received chemotherapy for ABC. Patients were randomized 2:1 to receive abemaciclib or placebo plus fulvestrant. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), pharmacokinetics (PK), health-related quality of life (HRQoL), and safety.
RESULTS
In Japan, 95 patients were randomized (abemaciclib, n = 64; placebo, n = 31). At final PFS analysis (February 14, 2017), median PFS was 21.2 and 14.3 months, respectively, in the abemaciclib and placebo groups (hazard ratio: 0.672; 95% confidence interval: 0.380-1.189). Abemaciclib had a higher objective response rate (37.5%) than placebo (12.9%). PK and safety profiles for Japanese patients were consistent with those of the overall population, without clinically meaningful differences across most HRQoL dimensions evaluated. The most frequent adverse events in the abemaciclib versus placebo groups were diarrhea (95.2 versus 25.8%), neutropenia (79.4 versus 0%), and leukopenia (66.7 versus 0%). At a second data cutoff (June 20, 2019), median OS was not reached with abemaciclib and 47.3 months with placebo (hazard ratio: 0.755; 95% confidence interval: 0.390-1.463).
CONCLUSIONS
Results of the Japanese subpopulation were consistent with the improved clinical outcomes and manageable safety profile observed in the overall population.
CLINICAL TRIAL REGISTRATION
NCT02107703; U.S. National Library of Medicine: https://clinicaltrials.gov/ct2/show/NCT02107703 .
背景
这是 MONARCH 2 研究的日本亚组分析，该研究是一项双盲、随机、安慰剂对照、III 期研究，评估了 abemaciclib 联合氟维司群在激素受体阳性、人表皮生长因子受体 2 阴性的晚期乳腺癌（ABC）患者中的疗效。
方法
符合条件的女性患者为在（新）辅助内分泌治疗（ET）后进展，或在辅助 ET 结束后≤12 个月内进展，或在 ABC 的一线 ET 中进展，且未接受过 ABC 的化疗。患者按 2:1 随机分组，分别接受 abemaciclib 或安慰剂联合氟维司群治疗。主要终点为无进展生存期（PFS）。次要终点包括总生存期（OS）、药代动力学（PK）、健康相关生活质量（HRQoL）和安全性。
结果
在日本，95 例患者被随机分组（abemaciclib，n=64；安慰剂，n=31）。在最终的 PFS 分析（2017 年 2 月 14 日）时，abemaciclib 组和安慰剂组的中位 PFS 分别为 21.2 和 14.3 个月（风险比：0.672；95%置信区间：0.380-1.189）。abemaciclib 的客观缓解率（37.5%）高于安慰剂（12.9%）。日本患者的 PK 特征和总体人群一致，在大多数评估的 HRQoL 维度上无临床意义的差异。abemaciclib 组比安慰剂组更常见的不良反应为腹泻（95.2% vs. 25.8%）、中性粒细胞减少（79.4% vs. 0%）和白细胞减少（66.7% vs. 0%）。在第二次数据截止（2019 年 6 月 20 日）时，abemaciclib 组未达到中位 OS，而安慰剂组为 47.3 个月（风险比：0.755；95%置信区间：0.390-1.463）。
结论
日本亚组的结果与总体人群中观察到的改善的临床结局和可管理的安全性特征一致。
临床试验注册
NCT02107703；美国国立医学图书馆：https://clinicaltrials.gov/ct2/show/NCT02107703。
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