背景：MONALEESA-3 III 期试验（NCT02422615）之前在统计学上显示，细胞周期蛋白依赖性激酶 4/6 抑制剂（CDK4/6i）RIB 联合 FUL 与安慰剂（PBO）联合 FUL 比在绝经后 HR+/HER2-的 ABC 患者一线（1L）或者二线（2L）治疗中可显着改善 OS（中位，未达到 vs40.0mo；危险比[HR]，0.72；95％CI，0.57-0.92，P=.00455）。根据研究方案，该分析是最终结果；在这项研究揭盲之后，仍在 PBO 组中接受研究治疗的患者可以交叉到 RIB 组。我们报告了对 OS 进行额外中位 16.9 个月的随访后的探索性分析，从而可以进一步证明 RIB 的长期生存获益。

Background:The Phase III MONALEESA-3 trial (NCT02422615) previously demonstrated a statistically significant improvement in OS with RIB, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), plus FUL compared with placebo (PBO) plus FUL as first-line (1L) or second-line (2L) treatment in postmenopausal pts with HR+/HER2-ABC (median, not reached vs 40.0 mo; hazard ratio [HR], 0.72; 95% CI, 0.57-0.92, P =.00455). This analysis was final per the protocol; following the unblinding of the study, pts still on study treatment in the PBO arm were allowed to cross over to the RIB arm. We report an exploratory analysis of OS after an additional median 16.9 mo of follow-up, allowing for further characterization of long-term survival benefits of RIB.

方法：HR+/HER2-绝经后 ABC 患者以 2：1 随机分配接受 RIB+FUL 或 PBO+FUL 进行 1L 和 2L治疗。采用 Cox 比例风险模型评估更新的 OS 并使用 Kaplan-Meier 方法进行了总结。其他进展后终点，例如无进展生存期 2（PFS2），开始化疗的时间（CT）和无化疗生存期也进行了评估和总结。

Methods:Postmenopausal pts with HR+/HER2-ABC were randomized 2:1 to receive RIB+FUL or PBO+FUL in 1L and 2L settings. Updated OS was evaluated by Cox proportional hazards model and summarized using Kaplan-Meier methods. Additional postprogression endpoints such as progression-free survival 2 (PFS2), time to chemotherapy (CT), and CT-free survival were also evaluated and summarized.

结果：在数据截止（2020 年 10 月 30 日）时，中位随访时间为 56.3 个月（最小，52.7 个月），其中 68（14.0％）和 21（8.7％）名患者仍在接受治疗，分别在 RIB 和 PBO 组中。通过延长随访时间，RIB+FUL 与 PBO+FUL 相比继续显示出 OS 获益（中位，53.7vs41.5 月；HR，0.73；95％CI，0.59-0.90）。RIB+FUL 在 1L 中比 PBO+FUL 的 OS 有延长（中位，未达到 vs51.8 个月；HR，0.64；95％CI，0.46-0.88）和 2L 亚组（中位，39.7vs33.7 个月；HR，0.78；95％CI，0.59-1.04）。亚组分析还显示，大多数亚组与意向性治疗（ITT）人群相比，OS 具有持续的获益。ITT 人群的PFS2，开始化疗的时间 CT 和无化疗生存期都倾向于 RIB+FUL（表）。在停止研究治疗的患者中，有 81.9％和 86.4％的患者随后接受了下一线治疗抗肿瘤治疗，在 RIB 组与 PBO 组分别有 14.0％和 30.0％的患者接受 CDK4/6i 作为后续治疗。没有观察到新的安全性信号。

Results:At the data cutoff (Oct 30, 2020), the median follow-up was 56.3 mo (min, 52.7 mo) and 68 (14.0%) and 21 (8.7%) patients were still on treatment in the RIB vs PBO arms, respectively. With this extended follow-up, RIB+FUL continued to demonstrate an OS benefit vs PBO+FUL (median, 53.7 vs 41.5 mo; HR, 0.73; 95% CI, 0.59-0.90). RIB + FUL had prolonged OS vs PBO+FUL in the 1L (median, not reached vs 51.8 mo; HR, 0.64; 95% CI, 0.46-0.88) and 2L subgroups (median, 39.7 vs 33.7 mo; HR, 0.78; 95% CI, 0.59-1.04). Subgroup analyses also showed a consistent OS benefit compared with the intent-to-treat (ITT) population for most subgroups. PFS2, time to CT, and CT-free survival for the ITT population favored RIB+FUL (Table). Among pts who discontinued study treatment, 81.9% and 86.4% received a next-line subsequent antineoplastic therapy, while 14.0% and 30.0% received a CDK4/6i as any subsequent line in the RIB vs PBO arms, respectively. No new safety signals were observed.

结论：对 HR+/HER2-绝经后 ABC 患者进行了将近 5 年的随访后，与 PBO+FUL 相比，RIB+FUL先前被证实的稳固且具有临床意义的 OS 获益仍然得以维持。在 1L 和 2L 亚组中均观察到使用RIB 的 OS 获益，这进一步支持了在这些亚组人群中使用 RIB。结果还表明，在 RIB 与 PBO 组后续开始化疗的时间明显延迟。

Conclusions:The previously demonstrated robust and clinically meaningful OS benefit with RIB + FUL compared with PBO+FUL was maintained after almost 5 years of follow-up in postmenopausal pts with HR+/HER2-ABC. The OS benefit of RIB was observed in the 1L and 2L subgroups, which further supports the use of RIB in these populations. The results also demonstrated a significant delay in the use of subsequent CT with RIB vs PBO.