In MONARCH 2, abemaciclib plus fulvestrant significantly improved median progression-free survival (PFS, 16.4 vs 9.3 months, hazard ratio [HR] 0.553) and overall survival (OS, 46.7 vs 37.3 months; HR 0.757) compared with placebo plus fulvestrant in hormone receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative) advanced breast cancer (ABC) patients who were endocrine therapy (ET) resistant, regardless of menopausal status. Here, we report findings in the premenopausal subgroup of the MONARCH 2 trial. The premenopausal subgroup included patients with natural menstrual bleeding who received a gonadotropin-releasing hormone agonist at least 4 weeks prior to study treatment start date and for the entire study duration. Of the 669 patients enrolled in the MONARCH 2 trial, 114 were premenopausal (abemaciclib plus fulvestrant, n = 72; placebo plus fulvestrant, n = 42), and were included in this analysis. The primary objective was investigator-assessed PFS and secondary objectives were OS, objective response rate, and safety and tolerability. Exploratory analyses included time to second disease progression (PFS2), time to chemotherapy (TTC), and chemotherapy-free survival (CFS). At the primary objective cutoff (February 14, 2017), median PFS was not reached for the abemaciclib plus fulvestrant arm versus 10.52 months for the placebo plus fulvestrant arm (HR 0.415; 95% CI 0.246–0.698). At the pre-specified OS interim cutoff (20-June-2019), median PFS was 28.6 months in the abemaciclib plus fulvestrant arm compared with 10.26 months in the placebo plus fulvestrant arm (HR 0.477; 95% CI 0.302–0.755). A numerical OS benefit was observed with abemaciclib plus fulvestrant compared to fulvestrant alone (HR 0.689; 95% CI 0.379–1.252, median, not reached vs 47.3 months). Improvements were also observed for the exploratory outcomes of PFS2 (HR 0.599), TTC (HR 0.674), and CFS (HR 0.642) with the addition of abemaciclib to fulvestrant. The safety profile was generally consistent with results disclosed previously. Results of the premenopausal subgroup in the MONARCH 2 trial were consistent with the improved clinical outcomes observed in the intent-to-treat population. The analysis provides support for the use of abemaciclib plus fulvestrant (with ovarian suppression) as an effective treatment option for premenopausal patients with HR+, HER2- ABC who are ET-resistant. Clinical trial registration: NCT02107703. Registered April 08, 2014- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02107703 .

中文翻译：

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Abemaciclib 加氟维司群治疗绝经前女性激素受体阳性、人表皮生长因子受体 2 阴性晚期乳腺癌：来自 MONARCH 2 试验的亚组分析

在 MONARCH 2 中，与安慰剂加氟维司群相比，abemaciclib 加氟维司群显着改善了中位无进展生存期（PFS，16.4 个月对 9.3 个月，风险比 [HR] 0.553）和总生存期（OS，46.7 对 37.3 个月；HR 0.757）受体阳性（HR 阳性）、人类表皮生长因子受体 2 阴性（HER2 阴性）的晚期乳腺癌（ABC）患者，无论是否绝经，内分泌治疗（ET）耐药。在这里，我们报告了 MONARCH 2 试验绝经前亚组的结果。绝经前亚组包括在研究治疗开始日期前至少 4 周和整个研究期间接受促性腺激素释放激素激动剂治疗的自然月经出血患者。在参加 MONARCH 2 试验的 669 名患者中，114 名绝经前患者（abemaciclib 加氟维司群，n = 72；安慰剂加氟维司群，n = 42），并被纳入该分析。主要目标是研究者评估的 PFS，次要目标是 OS、客观反应率以及安全性和耐受性。探索性分析包括至第二次疾病进展时间 (PFS2)、至化疗时间 (TTC) 和无化疗生存期 (CFS)。在主要目标截止点（2017 年 2 月 14 日），abemaciclib 加氟维司群的中位 PFS 未达到，而安慰剂加氟维司群的中位 PFS 为 10.52 个月（HR 0.415；95% CI 0.246–0.698）。在预先指定的 OS 中期截止点（2019 年 6 月 20 日），abemaciclib 加氟维司群的中位 PFS 为 28.6 个月，而安慰剂加氟维司群的中位 PFS 为 10.26 个月（HR 0.477；95% CI 0.302–0.755）。与单独使用氟维司群相比，abemaciclib 加氟维司群观察到了数值 OS 益处（HR 0.689；95% CI 0.379–1.252，中位数，未达到 vs 47.3 个月）。在氟维司群中添加 abemaciclib 后，还观察到 PFS2 (HR 0.599)、TTC (HR 0.674) 和 CFS (HR 0.642) 的探索性结果有所改善。安全性概况与之前披露的结果基本一致。MONARCH 2 试验中绝经前亚组的结果与在意向治疗人群中观察到的改善的临床结果一致。该分析支持使用 abemaciclib 加氟维司群（具有卵巢抑制）作为对 ET 耐药的 HR+、HER2-ABC 绝经前患者的有效治疗选择。临床试验注册：NCT02107703。4 月 8 日注册，