Jia Xiaomeng, Wang Kainan, Wang Xueqing, Luo Yiyang, Liu Huixin, Zhao Zuowei, Zhao Jinbo, Li Man
The Second Hospital of Dalian Medical University, Dalian, China.
Dalian Central Hospital, Dalian, China.
Ther Adv Med Oncol. 2025 Jun 6;17:17588359251336623. doi: 10.1177/17588359251336623. eCollection 2025.
There is no recognized optimal second-line treatment option for advanced hormone receptor-positive (HR+) breast cancer patients with CDK4/6 inhibitor (CDK4/6i) resistance.
This work aims to identify the optimal treatment option by evaluating the efficacy of various second-line treatment options in CDK4/6i-pretreated HR+ advanced breast cancer. Subgroup analyses aim to discuss how different genetic backgrounds and clinical characteristics influence the efficacy.
A systematic review and network meta-analysis (NMA) was designed.
A comprehensive search was conducted in Medline, Embase, and Cochrane Library for randomized controlled trials (RCTs). The primary outcome was progression-free survival (PFS), with subgroup analysis based on visceral metastasis and ESR1 mutations. Secondary outcomes were overall survival (OS), overall response rate (ORR), and clinical benefit rate (CBR). Bayesian NMA was conducted using GeMTC in R, with hazard ratios and 95% confidence intervals as effect measures.
Our analysis included 19 clinical trials involving 13 different treatment regimens ( = 6621), with 14 studies ( = 3876) reporting subgroup results for CDK4/6i-pretreated patients. Results showed that the combination of CDK4/6i and fulvestrant (Ful) was the most effective regimen for improving PFS in CDK4/6i-pretreated HR+ advanced breast cancer patients. Further subgroup analyses of visceral metastasis and ESR1 mutations consistently confirmed this finding. For OS, the combination of Bcl-2 inhibitor (Bcl-2i) and Ful was most favorable. In terms of ORR and CBR, selective estrogen receptor degraders (SERD) and CDK4/6i + ET were the most beneficial, respectively, with no significant differences among regimens in direct comparisons.
Our analysis reveals CDK4/6i + Ful is the most effective treatment option for CDK4/6i-pretreated HR+ advanced breast cancer, particularly in patients with visceral metastases or ESR1 mutations. In addition, Bcl-2i + Ful and SERD may be potential second-line strategy options.
This meta-analysis was registered in PROSPERO (CRD42024518926).
对于对细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i）耐药的晚期激素受体阳性（HR+）乳腺癌患者，尚无公认的最佳二线治疗方案。
本研究旨在通过评估各种二线治疗方案在接受CDK4/6i预处理的HR+晚期乳腺癌中的疗效，确定最佳治疗方案。亚组分析旨在探讨不同基因背景和临床特征如何影响疗效。
设计了一项系统评价和网状Meta分析（NMA）。
在Medline、Embase和Cochrane图书馆全面检索随机对照试验（RCT）。主要结局为无进展生存期（PFS），并基于内脏转移和ESR1突变进行亚组分析。次要结局为总生存期（OS）、总缓解率（ORR）和临床获益率（CBR）。使用R语言中的GeMTC进行贝叶斯NMA，以风险比和95%置信区间作为效应量。
我们的分析纳入了19项临床试验，涉及13种不同治疗方案（n=6621），其中14项研究（n=3876）报告了接受CDK4/6i预处理患者的亚组结果。结果显示，CDK4/6i与氟维司群（Ful）联合使用是改善接受CDK4/6i预处理的HR+晚期乳腺癌患者PFS的最有效方案。对内脏转移和ESR1突变的进一步亚组分析一致证实了这一发现。对于OS，Bcl-2抑制剂（Bcl-2i）与Ful联合使用最为有利。在ORR和CBR方面，选择性雌激素受体降解剂（SERD）和CDK4/6i+内分泌治疗（ET）分别最有益，在直接比较中各方案之间无显著差异。
我们的分析表明，CDK4/6i+Ful是接受CDK4/6i预处理的HR+晚期乳腺癌最有效的治疗方案，尤其适用于有内脏转移或ESR1突变的患者。此外，Bcl-2i+Ful和SERD可能是潜在的二线治疗策略选择。
本Meta分析已在PROSPERO（CRD42024518926）注册。
