背景:三种CDK4/6抑制剂的临床选择提出了一个具有挑战性的问题,由于缺乏明显的临床病例特征,生物标志物,以及它们在无进展生存期和总生存期方面的可比临床益处为临床治疗决策提供信息,我们对CDK4/6抑制剂联合内分泌治疗与风险比+/HER2-乳腺癌相关的不良事件进行了全面评估.方法:我们搜索了Cochrane,PubMed,Embase,和WebofScience数据库从成立到2022年8月1日。对研究结果进行了叙述总结,我们评估了方法学质量,报告质量,AMSTAR-2、PRISMA、和等级。结果:我们的分析包括24项荟萃分析系统评价,评估了13例早期乳腺癌(EBC)和158例晚期乳腺癌的AE质量。发现添加CDK4/6抑制剂可显着增加早期乳腺癌中任何级别的AE和3级或更高的AE,随着治疗中止的风险显着增加。在晚期乳腺癌中,高质量和中等质量的证据表明,CDK4/6抑制剂显著增加了所有级别的不良事件,包括3/4级不良事件,白细胞减少症,3/4级白细胞减少症,中性粒细胞减少症,3/4级中性粒细胞减少症,贫血,3/4级贫血,恶心,3/4级便秘,疲劳,发热,静脉血栓栓塞性腹痛,还有咳嗽.然而,他们没有显著提高3/4级腹泻的发病率.亚组分析显示palbociclib主要增加血液学毒性,尤其是3/4级中性粒细胞减少症,贫血,和血小板减少症.Ribociclib主要与3/4级中性粒细胞减少相关,QT间期延长,和脱发。Abemaciclib与腹泻和血肌酐水平升高密切相关。结论:与CDK4/6抑制剂相关的AE各不相同,需要个性化和精确的临床选择以实现最佳管理。这种方法应根据患者的病史和不同CDK4/6抑制剂的不同特征来改善患者的生活质量。系统审查注册:[https://systematicreview.gov/],标识符[CRD42022350167]。
Background: The clinical selection of three CDK4/6 inhibitors presents a challenging issue, owing to the absence of distinct clinical case characteristics, biomarkers, and their comparable clinical benefits in progression-free survival and overall survival To inform clinical treatment decisions, we conducted a comprehensive evaluation of the adverse events associated with CDK4/6 inhibitors in combination with endocrine therapy for hazard ratio+/HER2-breast cancer. Methods: We searched Cochrane, PubMed, Embase, and Web of Science databases from their inception until 1 August 2022. The results were summarized narratively, and we assessed the methodological quality, reporting quality, and evidence quality of AEs by AMSTAR-2, PRISMA, and GRADE. Results: Our analysis included 24 meta-analyses systematic reviews that evaluated the quality of AEs in 13 cases of early breast cancer (EBC) and 158 cases of advanced breast cancer The addition of CDK4/6 inhibitors was found to significantly increase AEs of any grade and AEs of grade 3 or higher in early breast cancer, along with a significant increase in the risk of treatment discontinuation. In advanced breast cancer, high and moderate-quality evidence indicated that CDK4/6 inhibitors significantly increased AEs across all grades, including grade 3/4 AEs, leucopenia, grade 3/4 leucopenia, neutropenia, grade 3/4 neutropenia, anemia, grade 3/4 anemia, nausea, grade 3/4 constipation, fatigue, pyrexia, venous thromboembolism abdominal pain, and cough. However, they did not significantly elevate the incidence of grade 3/4 diarrhea. Subgroup analysis revealed that palbociclib primarily increased hematologic toxicity, particularly grade 3/4 neutropenia, anemia, and thrombocytopenia. Ribociclib was mainly associated with grade 3/4 neutropenia, prolonged QT interval, and alopecia. Abemaciclib was closely linked with diarrhea and elevated blood creatinine levels. Conclusion: The AEs associated with CDK4/6 inhibitors vary, necessitating individualized and precise clinical selection for optimal management. This approach should be based on the patient\'s medical history and the distinct characteristics of different CDK4/6 inhibitors to improve the patient\'s quality of life. Systematic
Review Registration: [https://systematicreview.gov/], identifier [CRD42022350167].