ObjectiveTo systematically review the efficacy and safety of CDK4/6 inhibitors combined with endocrine therapy for advanced breast cancer.MethodsPubMed, EMBase, The Cochrane Library, CNKI, WanFang Data and VIP databases were electronically searched to collect randomized controlled trials (RCTs) of CDK4/6 inhibitors combined with endocrine therapy for advanced breast cancer from inception to October 13th, 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 4 RCTs involving 2 524 patients were included. The results of meta-analysis showed that: compared with placebo combined with endocrine therapy, CDK4/6 inhibitors combined with endocrine therapy could improve the median progression free survival rate (RR=0.53, 95%CI 0.47 to 0.60, P<0.000 01) and the objective response rate (RR=1.67, 95%CI 1.47 to 1.91,P<0.000 01). While there was no statistical difference in clinical benefit rate (RR=0.59, 95%CI 0.75 to 1.19,P=0.64). In terms of adverse reactions, CDK4/6 inhibitors combined with endocrine therapy had higher rates of neutropenia (RR=49.76, 95%CI 26.85 to 90.21, P<0.000 01), leukopenia (RR=48.69, 95%CI 18.74 to 133.61,P<0.000 01), fatigue (RR=3.11, 95%CI 1.37 to 7.08,P=0.007) and anemia (RR=2.96, 95%CI 1.61 to 5.42, P=0.000 3). There were no significant differences between two groups in nausea, diarrhea and decreased appetite.ConclusionCDK4/6 inhibitors combined with endocrine therapy for the patients with advanced breast cancer can improve median progression free survival and objective response rate, while increase the incidence of adverse events such as neutropenia, leukopenia, fatigue and anemia. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.
Objective To systematically review the efficacy and safety of CDK4/6 inhibitors in combination with endocrine therapy for HR+/HER2‒ breast cancer. Methods The PubMed, Cochrane Library, Web of Science, WanFang Data, CNKI, American Society of Clinical Oncology (ASCO), European Society of Medical Oncology (ESMO) and San Antonio Breast Cancer Symposium (SABCS) databases were electronically searched to collect randomized controlled trials on CDK4/6 inhibitors in combination with endocrine therapy for HR+/HER2‒ breast cancer from inception to July 5, 2023. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Meta-analysis was then performed using RevMan 5.4 software and Stata 14.0 software. Results A total of 8 studies involving 4 580 patients were included. The results of meta-analysis showed that overall survival and progression-free survival were significantly longer in the combination therapy group than those in the endocrine therapy alone group (HR=0.80, 95%CI 0.73 to 0.89, P<0.05; HR=0.54, 95%CI 0.50 to 0.59, P<0.05). The results also showed that patients in the combination therapy group also had significantly higher rates of objective remission and clinical benefit than those in the endocrine therapy group alone (RR=1.47, 95%CI 1.34 to 1.62, P<0.05; RR=1.20, 95%CI 1.11 to 1.30, P<0.05). In addition, the combination treatment group also increased the incidence of haematological toxicity such as neutropenia and leucopenia, but the differences in the incidence of nausea, diarrhoea and headache were not statistically significant between the two groups. Conclusion The combination of CDK4/6 inhibitors with endocrine therapy for HR+/HER2‒ breast cancer patients improve overall survival, progression-free survival, clinical benefit rate and objective remission rate, with significant long-term and near-term efficacy; however, this regimen increased the incidence of several adverse effects, and clinical use should be considered when considering the occurrence of serious adverse effects.
Objective To compare the efficacy and safety of different cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) for the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer using network meta-analysis. Methods Randomized controlled trials (RCTs) on CDK4/6i for the treatment of HR+/HER2- metastatic/advanced breast cancer were retrieved from databases including PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, Wanfang, VIP, and SinoMed, with the search period ranging from database inception to August 2023. Bayesian network meta-analysis was conducted using R 4.2.0 software. Results A total of 18 RCTs from 25 publications, involving 8 031 patients and 11 treatment regimens, were included. There were no significant differences in progression-free survival (PFS) and overall survival (OS) among different CDK4/6i+ET combinations. The highest cumulative probability for PFS was observed with dalpiciclib (DAL)+fulvestrant (FUL), while ribociclib (RIB)+FUL ranked first for OS. In terms of efficacy, abemaciclib (ABE)+aromatase inhibitors (AI) and ABE+FUL ranked first in objective response rate and clinical benefit rate, respectively. Regarding safety, statistically significant differences (P<0.05) in grade 3-4 adverse events and serious adverse events were observed among certain types of CDK4/6i. Conclusion Current evidence suggests that CDK4/6i+ET is superior to ET alone for the treatment of HR+/HER2- advanced/metastatic breast cancer. Different CDK4/6i+ET combinations demonstrate comparable or similar efficacy; however, the incidence of adverse reactions is higher with combination therapy. Treatment regimens should be selected based on individual patient conditions.