在 MONALEESA-3 期随机对照试验中，对于激素受体阳性、人表皮生长因子受体 2 阴性的绝经后妇女的晚期乳腺癌，来曲唑联合氟维司群治疗：更新的总生存数据。

Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival.

机构信息

David Geffen School of Medicine at UCLA, Los Angeles, USA.

Multidisciplinary Breast Centre, Universitair Ziekenhuis Leuven, Leuven, Belgium.

出版信息

Ann Oncol. 2021 Aug;32(8):1015-1024. doi: 10.1016/j.annonc.2021.05.353. Epub 2021 Jun 5.

DOI:10.1016/j.annonc.2021.05.353

PMID:34102253

Abstract

BACKGROUND

Ribociclib plus fulvestrant demonstrated significant progression-free survival (PFS) and overall survival (OS) benefits in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). Here we present a new landmark in survival follow-up for a phase III cyclin-dependent kinases 4 and 6 inhibitor clinical trial in patients with ABC (median, 56.3 months).

PATIENTS AND METHODS

This phase III, randomized, double-blind, placebo-controlled trial was conducted at 174 sites (30 countries). Patients were men and postmenopausal women (age ≥18 years) with histologically/cytologically confirmed HR+/HER2- ABC. Patients could have received ≤1 line of endocrine therapy (ET) but no chemotherapy for ABC. Patients, assigned 2:1, were stratified by the presence/absence of liver/lung metastases and previous ET. Patients received intramuscular fulvestrant (500 mg, day 1 of each 28-day cycle plus day 15 of cycle 1) with oral ribociclib (600 mg/day, 3 weeks on, 1 week off) or placebo. Efficacy analyses were by intention to treat. Safety was assessed in patients receiving ≥1 dose study treatment. OS was a secondary endpoint. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615; no longer enrolling).

RESULTS

Between 18 June 2015 and 10 June 2016, 726 patients were randomly assigned (484, ribociclib; 242, placebo). At data cut-off (30 October 2020), median OS (mOS) was 53.7 months (ribociclib) versus 41.5 months (placebo) [hazard ratio (HR), 0.73; 95% confidence interval (CI) 0.59-0.90]. Subgroup analyses were consistent with overall population. In the first-line setting, most patients in the ribociclib arm (∼60%) lived longer than median follow-up; mOS was 51.8 months in the placebo arm (HR, 0.64; 95% CI 0.46-0.88). In the second-line setting, mOS was 39.7 months (ribociclib) versus 33.7 months (placebo) (HR, 0.78; 95% CI 0.59-1.04). No apparent drug-drug interaction between ribociclib and fulvestrant or new safety signals were observed.

CONCLUSIONS

This analysis reported extended OS follow-up in MONALEESA-3. mOS was ∼12 months longer in patients with HR+/HER2- ABC treated with ribociclib plus fulvestrant compared with fulvestrant monotherapy.

摘要

背景

在激素受体阳性、人表皮生长因子受体 2 阴性（HR+/HER2-）晚期乳腺癌（ABC）患者中，瑞博西利联合氟维司群显著改善了无进展生存期（PFS）和总生存期（OS）。这里我们报道了一项针对 ABC 患者的 III 期细胞周期蛋白依赖性激酶 4 和 6 抑制剂临床试验的新生存随访里程碑（中位随访时间为 56.3 个月）。

患者和方法

这项 III 期、随机、双盲、安慰剂对照试验在 174 个地点（30 个国家）进行。患者为组织学/细胞学确认的 HR+/HER2-ABC 的男性和绝经后女性（年龄≥18 岁）。患者可接受≤1 线内分泌治疗（ET），但不能接受 ABC 的化疗。患者按有无肝/肺转移和先前 ET 按 2:1 分层。患者接受肌肉注射氟维司群（500mg，每 28 天周期的第 1 天，第 1 周期的第 15 天）联合口服瑞博西利（600mg/天，连续服用 3 周，停药 1 周）或安慰剂。疗效分析采用意向治疗。接受至少 1 剂研究治疗的患者进行安全性评估。OS 是次要终点。MONALEESA-3 在 ClinicalTrials.gov 注册（NCT02422615；不再入组）。

结果

2015 年 6 月 18 日至 2016 年 6 月 10 日，726 例患者被随机分配（484 例，瑞博西利；242 例，安慰剂）。截至数据截止日期（2020 年 10 月 30 日），中位 OS（mOS）为 53.7 个月（瑞博西利）与 41.5 个月（安慰剂）[风险比（HR），0.73；95%置信区间（CI）0.59-0.90]。亚组分析与总体人群一致。在一线治疗中，瑞博西利组中约 60%的大多数患者生存期超过中位随访时间；安慰剂组的 mOS 为 51.8 个月（HR，0.64；95%CI 0.46-0.88）。在二线治疗中，mOS 为 39.7 个月（瑞博西利）与 33.7 个月（安慰剂）（HR，0.78；95%CI 0.59-1.04）。未观察到瑞博西利与氟维司群之间存在药物相互作用或新的安全性信号。