Efficacy of CDK4/6 inhibitors combined with endocrine therapy in HR+/HER2− breast cancer: an umbrella review

• Published in: Journal of cancer research and clinical oncology Vol. 150; no. 1; p. 16
• Main Authors: Pu, Dongqing, Xu, Debo, Wu, Yue, Chen, Hanhan, Shi, Guangxi, Feng, Dandan, Zhang, Mengdi, Liu, Zhiyong, Li, Jingwei
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.01.2024; Springer Nature B.V
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast cancer; Breast Neoplasms; Cancer Research; Chemotherapy; Cyclin-dependent kinase 4; Cyclin-Dependent Kinase 4 - antagonists & inhibitors; Cyclin-Dependent Kinase 6 - antagonists & inhibitors; Cyclin-dependent kinases; Disease-Free Survival; Endocrine therapy; ErbB-2 protein; Female; Hematology; Humans; Internal Medicine; Kinases; Medicine; Medicine & Public Health; Meta-analysis; Oncology; Progression-Free Survival; Protein Kinase Inhibitors - therapeutic use; Receptor, ErbB-2; Review; Survival; Endocrine therapy; Meta-analysis and systematic review; Breast cancer; Umbrella review; Clinical efficacy; CDK4/6 inhibitor
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-023-05516-1

Background 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. Methods 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. Results 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. Conclusions 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.