First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China.
College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
J Cancer Res Clin Oncol. 2024 Jan 19;150(1):16. doi: 10.1007/s00432-023-05516-1.
The use of Cyclin-Dependent kinase 4 and 6 (CDK4/6) inhibitors has profoundly changed the challenge of endocrine therapy (ET) resistance in hormone receptor-positive (HR+)/HER2-negative (HER2-) breast cancer. However, there is currently no comprehensive evaluation of the evidence for the efficacy of CDK4/6 inhibitors. We conducted an umbrella review to explore the impact of CDK4/6 inhibitor combined with ET on breast cancer by summarizing and assessing the meta-analysis (MA) and systematic review (SR) evidence.
Cochrane, PubMed, Embase, and Web of Science databases were searched from inception to August 1st, 2022. Eligible studies were assessed for methodological quality, report quality, and evidence quality using the AMSTAR-2 scale, PRISMA 2020, and GRADE grading systems, respectively. We summarized all efficacy outcomes of CDK4/6 inhibitors for breast cancer and reported them in narrative form.
Our study included 24 MAs and SRs. The strongest evidence demonstrated that CDK4/6 inhibitor combined with ET significantly improved progression-free survival (PFS), overall survival (OS) in advanced breast cancer (ABC). A large body of moderate to high evidence showed a significant association between combination therapy and objective response rate (ORR), and clinical benefit response (CBR) benefit in ABC. Low evidence suggested some degree of benefit from combination therapy in second progression-free survival (PFS2) and time to subsequent chemotherapy (TTC) outcomes in ABC and invasive disease-free survival (IDFS) outcomes in early breast cancer.
Based on current evidence, CDK4/6 inhibitors combined with ET have great confidence in improving PFS, OS, ORR, and CBR outcomes in patients with ABC, which provides more rational and valid evidence-based medicine for CDK4/6 inhibitor promotion and clinical decision support.
细胞周期蛋白依赖性激酶 4 和 6（CDK4/6）抑制剂的使用极大地改变了激素受体阳性（HR+）/人表皮生长因子受体 2 阴性（HER2-）乳腺癌内分泌治疗（ET）耐药的挑战。然而，目前尚无对 CDK4/6 抑制剂疗效证据的全面评估。我们进行了伞式综述，通过总结和评估荟萃分析（MA）和系统评价（SR）证据，探讨 CDK4/6 抑制剂联合 ET 对乳腺癌的影响。
从成立到 2022 年 8 月 1 日，我们在 Cochrane、PubMed、Embase 和 Web of Science 数据库中进行了搜索。使用 AMSTAR-2 量表、PRISMA 2020 和 GRADE 分级系统分别评估合格研究的方法学质量、报告质量和证据质量。我们总结了 CDK4/6 抑制剂治疗乳腺癌的所有疗效结果，并以叙述形式报告。
我们的研究包括 24 项 MA 和 SR。最强的证据表明，CDK4/6 抑制剂联合 ET 显著改善了晚期乳腺癌（ABC）的无进展生存期（PFS）和总生存期（OS）。大量中等至高度证据表明，联合治疗与 ABC 的客观缓解率（ORR）和临床获益反应（CBR）获益之间存在显著关联。低证据表明，联合治疗在 ABC 的第二次无进展生存期（PFS2）和随后化疗时间（TTC）结局以及早期乳腺癌的无侵袭性疾病生存期（IDFS）结局方面具有一定程度的获益。
基于目前的证据，CDK4/6 抑制剂联合 ET 对改善 ABC 患者的 PFS、OS、ORR 和 CBR 结局具有很大信心，为 CDK4/6 抑制剂的推广和临床决策支持提供了更合理、更有效的循证医学证据。
