Efficacy and safety of CDK4/6 inhibitors combined with endocrine therapy versus endocrine therapy alone in hormone receptor-positive, HER2-negative, advanced breast cancer: a systematic review and meta-analysis

Abstract

Background: In previous studies on the application of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy in advanced breast cancer, the outcomes of overall survival (OS) were inconsistent. This systematic review and meta-analysis aimed to further evaluate the clinical efficacy and safety of CDK4/6 inhibitors combined with endocrine therapy on patients with hormone receptor (HR)positive and human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer.Methods: Randomized controlled trials (RCTs) comparing CDK4/6 inhibitors plus endocrine therapy and endocrine therapy alone in patients with HR-positive and HER2-negative advanced breast cancer were searched in the databases of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), WANFANG and China Science and Technology Journal Database (VIP) up to November 2022.Hazard ratios (HRs) and confidence intervals (CI) of OS, progression-free survival (PFS), the time from randomization to the first recorded disease progression while the patient was receiving next-line therapy or death from any cause (PFS2), time to first subsequent chemotherapy after discontinuation (TTC), and objective response rate (ORR), clinical benefit rate (CBR), safety indicators were extracted. Stata 14.0 software was used for meta analysis and the Cochrane risk-of-bias tool 2.0 was used to evaluate the bias risk.

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

“…For HR+/HER2− ABC, there was broad agreement in the MAs findings that CDK4/6 inhibitors were associated with significant improvements in PFS, OS, ORR, and CBR, affirming the short- and long-term clinical efficacy of combination therapy for ABC. Notably, Munzone et al ( 2021 ) looked at PFS2 and TTC outcomes and found that combination therapy improved PFS2 and TTC, which was consistent with the results of a MA published during the review of this study (Dai et al 2022 ), suggesting that combination therapy may delay the onset of endocrine resistance and delay the duration of chemotherapy and chemotherapy-related toxicity, which may translate into a significant OS benefit and maintain a better quality of life for patients over a longer period of time.…”

Dynamic Projection of Medication Nonpersistence and Nonadherence Among Patients With Early Breast Cancer

“…The development of oral endocrine drugs has significantly improved the therapeutic strategy for breast cancer, providing patients with convenient and effective alternatives to traditional intravenous chemotherapy. 1 However, despite their benefits, adherence to and persistence of oral anticancer treatments remain a major challenge. 2 Adherence refers to the degree to which patients adhere to their prescribed medication regimen, while persistence refers to the length of time patients continue to take their medication as directed.…”

Comparative efficacy and safety of CDK4/6 inhibitors combined with endocrine therapies for HR+/HER2-breast cancer: Systematic review and network meta-analysis

“…In recent years, the confluence of targeted drugs such as Cyclin-Dependent Kinase4/6 (CDK4/6) inhibitors with ET has emerged as a burgeoning area of research. Numerous randomized controlled trials (RCTs) have conclusively demonstrated that the combination of CDK4/6 inhibitors with ET effectively manages HR+/HER2-breast cancer, curtails the dissemination of cancer cells, and markedly improves patients' quality of life and survival rates [ [5] , [6] , [7] , [8] ].…”