CDK4/6 inhibitors plus endocrine therapy versus endocrine monotherapy in hormone receptor-positive, HER2-negative advanced breast cancer: a reconstructed individual patient data meta-analysis of phase 3 randomised controlled trials.

This meta-analysisaims to evaluate their effect on survival outcomes across clinically relevant subgroups.

本荟萃分析旨在评估它们在临床相关亚组中对生存结果的影响。

Methods

For this reconstructed individual patient-level meta-analysis, we searched PubMed, Web of Science, the Cochrane Library, and Scopus on June 2, 2025, for phase 3 trials that compared CDK4/6 inhibitors plus endocrine therapy with endocrine monotherapy in patients with hormone receptor-positive, HER2-negative advanced breast cancer.

在这项重建的个体患者水平的荟萃分析中，我们在2025年6月2日检索了PubMed、Web of Science、Cochrane图书馆和Scopus，以寻找比较CDK4/6抑制剂联合内分泌治疗与内分泌单药治疗在激素受体阳性、HER2阴性晚期乳腺癌患者中的III期试验。

Kaplan-Meier curves were reconstructed with the use of a time-to-event algorithm to retrieve survival data for individual patients.

使用时间到事件算法重建了Kaplan-Meier曲线，以检索个体患者的生存数据。

A series of pooled analyses for the reconstructed individual patient data were conducted with the use of a stratified Cox regression model.

使用分层Cox回归模型对重建的个体患者数据进行了一系列汇总分析。

A pairwise random-effects meta-analysiswas also conducted.

还进行了一项成对随机效应的荟萃分析。

Patients were stratified by endocrine sensitivity into endocrine-sensitive and endocrine-resistant, as well as by age, ethnicity, progesterone receptor status, menopausal status, Eastern Cooperative Oncology Group performance status, bone-only disease, and visceral metastasis.

患者根据内分泌敏感性分为内分泌敏感和内分泌耐药组，同时按照年龄、种族、孕激素受体状态、绝经状态、东部肿瘤协作组表现状态、仅骨疾病和内脏转移进行分层。

Primary outcomes analysed were progression-free survivaland overall survival. The protocol is registered in PROSPERO (CRD420251073444).

分析的主要结果是无进展生存期和总生存期。该研究方案已在PROSPERO注册，注册号为CRD420251073444。

Results

11 phase 3 trials, including 6035 patients and four agents-abemaciclib, ribociclib, palbociclib, and dalpiciclib-were included.

纳入了11项III期临床试验，共6035名患者，涉及四种药物：阿贝西利、利伯西利、帕博西利和达比加群。

CDK4/6 inhibitors plus endocrine therapy significantly improved progression-free survivalin both endocrine-sensitive (HR 0·57, 95% CI 0·52-0·63; p<0·0001) and endocrine-resistant cancers (0·51, 0·45-0·57; p<0·0001).

CDK4/6抑制剂联合内分泌治疗显著改善了内分泌敏感性癌症（HR 0.57，95% CI 0.52-0.63；p<0.0001）和内分泌耐药性癌症（HR 0.51，95% CI 0.45-0.57；p<0.0001）的无进展生存期。

Overall survivalwas also improved with CDK4/6 inhibitors plus endocrine therapy in both subgroups: endocrine-sensitive (0·83; 0·74-0·92; p=0·0005) and endocrine-resistant (0·77; 0·67-0·89; p=0·0003).

CDK4/6抑制剂联合内分泌治疗在两个亚组中也改善了总生存期：内分泌敏感组（0.83；95% 置信区间 0.74-0.92；p=0.0005）和内分泌耐药组（0.77；95% 置信区间 0.67-0.89；p=0.0003）。

All individual agents, when combined with endocrine therapy showed progression-free survivalbenefits: abemaciclib (HR 0·53, 95% CI 0·46-0·61; p<0·0001), ribociclib (0·60, 0·52-0·68; p<0·0001), palbociclib (0·56, 0·49-0·65; p<0·0001), and dalpiciclib (0·49, 0·40-0·61; p<0·0001).

所有单独使用的药物，当与内分泌治疗联合时，都显示出无进展生存期的益处：阿贝西利（HR 0.53，95% 置信区间 0.46-0.61；p<0.0001），利布西利（HR 0.60，95% 置信区间 0.52-0.68；p<0.0001），帕博西利（HR 0.56，95% 置信区间 0.49-0.65；p<0.0001），以及达利西利（HR 0.49，95% 置信区间 0.40-0.61；p<0.0001）。

However, only abemaciclib (0·79, 0·67-0·92; p=0·0031) and ribociclib (0·73, 0·64-0·84; p<0·0001) showed significant overall survivalbenefits; palbociclib did not reach statistical significance (0·89, 0·77-1·02; p=0·0920), and data for dalpiciclib remain immature.

然而，仅阿贝西利（0·79，95% 置信区间0·67-0·92；p=0·0031）和利博西利（0·73，95% 置信区间0·64-0·84；p<0·0001）显示出显著的总生存益处；帕博西利未达到统计学意义（0·89，95% 置信区间0·77-1·02；p=0·0920），而达利西利的数据尚不成熟。

Other clinically relevant subgroups, stratified by age, ethnicity, progesterone receptor status, menopausal status, Eastern Cooperative Oncology Group performance status, bone-only disease, and visceral metastasis, showed progression-free survivaland overall survivalbenefits in patients with endocrine-sensitive and endocrine-resistant tumours.

其他临床相关的亚组，根据年龄、种族、孕激素受体状态、绝经状态、东部肿瘤协作组表现状态、仅骨疾病和内脏转移进行分层，显示出内分泌敏感和内分泌抵抗肿瘤患者的无进展生存和总生存益处。

interpretation

CDK4/6 inhibitors plus endocrine therapy significantly improved survival in hormone receptor-positive, HER2-negative advanced breast cancer.

CDK4/6抑制剂联合内分泌治疗显著改善了激素受体阳性、HER2阴性的晚期乳腺癌患者的生存期。

Benefits in progression-free survivaland overall survivalwere consistent across major clinical subgroups.

在主要临床亚组中，无进展生存期和总生存期的获益是一致的。

Although all agents improved progression-free survival, only ribociclib and abemaciclib showed statistically significant overall survivalbenefits, whereas palbociclib did not, and data for dalpiciclib remain immature.

尽管所有药物均改善了无进展生存期，但只有利博西利和阿贝西利显示出统计学上显著的总生存获益，而帕博西利则没有，达立西利的数据尚不成熟。

Further head-to-head comparisons and assessments of toxicity profiles, as well as patient-reported outcomes, are needed.

需要进一步进行头对头的比较以及对毒性和患者报告结果的评估。

funding

None.

无。