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 compare the efficacy and safety of different cyclin-dependent kinase4/6 inhibitor (CDK4/6i) combined with endocrine therapy (ET) for HR+/HER2- advanced or metastatic breast cancer based on mesh meta-analysis. Methods Randomized controlled trials (RCTs) of CDK4/6i in the treatment of HR+/HER2- metastatic/advanced breast cancer were searched in PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases from inception to August 2023. Bayesian network meta-analysis was performed by R 4.2.0 software. Results Finally, 18 RCTs in 25 articles, covering 8 031 patients, involving 11 treatment regimens were included. There were no statistical differences in progression-free survival (PFS) or overall survival (OS) between CDK4/6i+ET combinations. DAL+FUL ranked first in PFS rate, and RIB+FUL ranked first in OS rate. In terms of effectiveness, ABE+AI and ABE+FUL ranked first in objective response rate (ORR) and clinical benefit rate (CBR), respectively. In terms of safety, there were significant differences in grade 3-4 AEs and SAE among some CDK4/6i types (P<0.05). Conclusion Current evidence shows that CDK4/6i+ET is superior to ET alone in the treatment of HR+/HER2- advanced/metastatic breast cancer, and different combinations of CDK4/6i+ET have the same or similar effects, but the combination has a higher incidence of adverse reactions, and a reasonable treatment plan should be selected according to the individual situation of patients.
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.