Multidisciplinary Breast Centre, Universitair Ziekenhuis Leuven, Herestraat 49, 3000, Leuven, Belgium.
University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Breast Cancer Res. 2023 Aug 31;25(1):103. doi: 10.1186/s13058-023-01701-9.
The phase III MONALEESA-3 trial included first- (1L) and second-line (2L) patients and demonstrated a significant overall survival (OS) benefit for ribociclib + fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) in the final protocol-specified and exploratory (longer follow-up) OS analyses. At the time of these analyses, the full OS benefit of 1L ribociclib was not completely characterized because the median OS (mOS) was not reached. As CDK4/6 inhibitor (CDK4/6i) + endocrine therapy (ET) is now a preferred option for 1L HR+/HER2- ABC, we report an exploratory analysis (median follow-up, 70.8 months; 14.5 months longer than the prior analysis) to fully elucidate the OS benefit in the MONALEESA-3 1L population.
Postmenopausal patients with HR+/HER2- ABC were randomized 2:1 to 1L/2L fulvestrant + ribociclib or placebo. OS in 1L patients (de novo disease or relapse > 12 months from completion of [neo]adjuvant ET) was assessed by Cox proportional hazards model and Kaplan-Meier methods. Progression-free survival 2 (PFS2) and chemotherapy-free survival (CFS) were analyzed. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615).
At data cutoff (January 12, 2022; median follow-up time, 70.8 months), mOS was 67.6 versus 51.8 months with 1L ribociclib versus placebo (hazard ratio (HR) 0.67; 95% CI 0.50-0.90); 16.5% and 8.6% of ribociclib and placebo patients, respectively, were still receiving treatment. PFS2 (HR 0.64) and CFS (HR 0.62) favored ribociclib versus placebo. Among those who discontinued treatment, 16.7% and 35.0% on ribociclib or placebo, respectively, received a subsequent CDK4/6i. No new safety signals were observed.
This analysis of MONALEESA-3 reports the longest mOS thus far (67.6 months) for 1L patients in a phase III ABC trial. These results in a 1L population show that the OS benefit of ribociclib was maintained through extended follow-up, further supporting its use in HR+/HER2- ABC.
III 期 MONALEESA-3 试验纳入了一线（1L）和二线（2L）患者，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，与安慰剂相比，接受瑞博西林联合氟维司群治疗可显著改善总生存期（OS），这在最终方案规定的和探索性（更长随访）OS 分析中得到证实。在这些分析时，由于中位 OS（mOS）尚未达到，1L 瑞博西林的完全 OS 获益尚未完全明确。由于 CDK4/6 抑制剂（CDK4/6i）联合内分泌治疗（ET）现在是 HR+/HER2-ABC 的首选方案，我们报告了一项探索性分析（中位随访 70.8 个月；比之前的分析长 14.5 个月），以充分阐明 MONALEESA-3 1L 人群的 OS 获益。
绝经后 HR+/HER2-ABC 患者以 2:1 的比例随机分配至 1L/2L 氟维司群联合瑞博西林或安慰剂。通过 Cox 比例风险模型和 Kaplan-Meier 方法评估 1L 患者（新发疾病或辅助 ET 完成后复发>12 个月）的 OS。无进展生存期 2（PFS2）和化疗无进展生存期（CFS）进行分析。MONALEESA-3 在 ClinicalTrials.gov 上注册（NCT02422615）。
数据截止日期（2022 年 1 月 12 日；中位随访时间 70.8 个月）时，1L 瑞博西林组 mOS 为 67.6 个月，安慰剂组为 51.8 个月（风险比（HR）0.67；95%CI 0.50-0.90）；分别有 16.5%和 8.6%的瑞博西林和安慰剂患者仍在接受治疗。PFS2（HR 0.64）和 CFS（HR 0.62）均有利于瑞博西林。在停止治疗的患者中，瑞博西林组分别有 16.7%和安慰剂组 35.0%的患者接受了后续 CDK4/6i 治疗。未观察到新的安全性信号。
这项 MONALEESA-3 分析报告了 III 期 ABC 试验中 1L 患者迄今为止最长的 mOS（67.6 个月）。1L 人群的这些结果表明，瑞博西林的 OS 获益通过延长随访时间得以维持，进一步支持其在 HR+/HER2-ABC 中的应用。
