Clinical benefit and safety profile of cross-line therapy with CDK4/6 inhibitors:a retrospective study of HR+/HER2–advanced breast cancer

Objective:CDK4/6 inhibitors(CDK4/6is)in combination with endocrine therapy have secured a central role in the treatment of hormone receptor(HR)-positive advanced breast cancer(ABC)and have transformed the therapeutic landscape.Cross-line CDK4/6i therapy in which another CDK4/6i is continued after progression on a prior CDK4/6i may still offer advantageous therapeutic effects.Cross-line CDK4/6i therapy is an area of active investigation in the ongoing pursuit to improve outcomes for patients with HR+/human epidermal growth factor receptor 2(HER2)–ABC.Methods:This retrospective study enrolled 82 patients with HR+/HER2–ABC who were treated with cross-line CDK4/6is(abemaciclib,palbociclib,ribociclib,and dalpiciclib)after progression with another CDK4/6i.The primary endpoint was progression-free survival(PFS)according to version 1.1 of the Response Evaluation Criteria in Solid Tumors.Secondary endpoints included toxicity,objective response rate,disease control rate,and overall survival.Adverse events(AEs)were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events,as promulgated by the U.S.Department of Health and Human Services.Results:Eighty-two HR+/HER2–ABC patients who received cross-line CDK4/6i therapy from January 2022 to February 2024 were enrolled.The median age of the patients was 60 years.The median PFS of all patients was 7.6 months(95%CI,5.9-9.2).Cox regression analysis identified lung metastasis and a switch to endocrine therapy following prior CDK4/6i therapy as independent predictive factors for PFS.Notably,patients who previously received abemaciclib and switched to palbociclib upon disease progression had a median PFS of 10.7 months.The strategy of transitioning to chemotherapy after progression on a prior CDK4/6i,then to a subsequent CDK4/6i merits further investigation.Hematologic toxicity was the most common grade≥3 AEs.No instances of fatal safety events were observed.Conclusions:Cross-line CDK4/6i therapy is associated with significant clinical benefits and manageable safety profiles in patients with HR+/HER2–ABC,which underscores cross-line CDK4/6i therapy potential as an effective treatment strategy.

CDK4/6抑制剂在HR^(+)晚期乳腺癌治疗中的耐药机制及进展后治疗策略

细胞周期蛋白依赖性激酶4/6(CDK4/6)抑制剂联合内分泌治疗已成为激素受体阳性(HR^(+))、人类表皮生长因子受体-2阴性(HER2^(-))乳腺癌患者的晚期一线及二线标准治疗方案。尽管CDK4/6抑制剂可实现有效的疾病控制,但对于晚期乳腺癌患者最终仍会因耐药出现疾病进展。目前CDK4/6抑制剂相关耐药机制尚不完全清楚,同时治疗失败后的最佳治疗策略仍是一个亟待解决的问题。本文就CDK4/6抑制剂的潜在耐药机制和后续治疗策略的最新研究进展做一综述。

LA-D-B1,a novel Abemaciclib derivative,exerts anti-breast cancer effects through CDK4/6

Background:Regulatory proteins involved in human cellular division and proliferation,cyclin-dependent kinases 4 and 6(CDK4/6)are overexpressed in numerous cancers,including triple-negative breast cancer(TNBC).TNBC is a common pathological subtype of breast cancer that is prone to recurrence and metastasis,and has a single treatment method.As one of the CDK4/6 inhibitors,abemaciclib can effectively inhibit the growth of breast tumors.In this study,we synthesized LA-D-B1,a derivative of Abemaciclib,and investigated its anti-tumor effects in breast cancer.Methods:Cellular viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Cell cloning and migration abilities were determined by colony formation assay and wound healing assay.Cell invasion abilities and adhesion were determined by cell invasion assay and cell adhesion assay.The impact of compound LA-D-B1 on cell proliferation and the cell cycle was analyzed through Western blotting,which quantified the levels of proteins associated with the cyclin-dependent kinase(CDK)4/6-cyclin D-Rb-E2F pathway.The in vivo anti-tumor activity of compound LA-D-B1 was investigated using a chick chorioallantoic membrane(CAM)model.Results:The study demonstrated that LA-D-B1 effectively suppressed breast cancer cell proliferation,induced apoptosis,and caused cell cycle arrest.Furthermore,LA-D-B1 reduced the expression of key proteins in the CDK4/6-cyclin D-Rb-E2F pathway,including CDK4,CDK6 and E2F1.The results also indicated significant antitumor activity of LA-D-B1 in a transplanted tumor model.Conclusion:In this study,LA-D-B1 demonstrated a potent anti-tumor effect by effectively suppressing cell proliferation and inhibiting cell cycle progression in breast cancer.These findings highlight the potential of LA-D-B1 as a valuable compound for enhancing therapeutic outcomes and controlling the progression of breast cancer.

基于FAERS数据库的周期蛋白依赖性激酶4/6抑制剂血液毒性真实世界研究

目的 基于美国美国食品药品管理局(FDA)的不良事件报告系统(FAERS)分析3种周期蛋白依赖性激酶4/6(CDK4/6)抑制剂上市后的不良事件(AEs)信号,为临床用药安全提供参考。方法 提取FAERS数据库2015年第一季度至2022年第一季度共29个季度AEs,利用报告比值比法(ROR)和比例报告比值法(PRR)对CDK4/6抑制剂AEs进行数据挖掘。结果 CDK4/6抑制剂相关性血液毒性报告共有7 872份,各抑制剂血液毒性AEs占总AEs比例依次为哌柏西利(80.31%)>瑞博西利(15.36%)>阿贝西利(4.33%)。血液毒性常见中性粒细胞减少和贫血。哌柏西利(2 982/6 322,47.17%)和瑞博西利(613/1 209,50.70%)致中性粒细胞减少的报告占比较阿贝西利(117/341,34.31%)更高,血液毒性主要发生在药物开始使用后60 d内(1 630,61.86%),哌柏西利中位时间最长,且用药90 d后仍有32.9%的患者存在血液毒性,不同CDK4/6抑制剂血液毒性临床表现及发生强度存在差异。结论 哌柏西利、阿贝西利、瑞博西利均会导致明显的血液毒性,其中阿贝西利致血液毒性报告最少,但要警惕阿贝西利致贫血后导致死亡的风险。用药后的2个月内密切监测全血细胞计数,关注中性粒细胞、血红蛋白等水平,警惕CDK4/6抑制剂相关血液AEs的发生。

Can cyclin-dependent kinase 4/6 inhibitors convert inoperable breast cancer relapse to operability? A case report

BACKGROUND Pathological complete response(pCR) is rare in hormone receptor-positive(HR+)HER2-negative breast cancer(BC) treated with either endocrine therapy(ET) or chemotherapy. Radical resection of locoregional relapse, although potentially curative in some cases, is challenging when the tumor invades critical structures.The oral cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with ET has obtained a significant increase in objective response rates and progression-free survival in patients with advanced BC and is now being evaluated in the neoadjuvant setting. We present a clinical case of a patient with an inoperable locoregional relapse of HR+ HER2-negative BC who experienced p CR after treatment with palbociclib.CASE SUMMARY We report the clinical case of a 60-year-old patient who presented with an inoperable locoregional relapse of HR+, HER2-negative BC 10 years after the diagnosis of the primary tumor. During a routine follow-up visit, breast magnetic resonance imaging and positron emission tomography/computed tomography revealed a 4-cm lesion in the right subclavicular region, infiltrating the chest wall and extending to the subclavian vessels, but without bone or visceral involvement. Treatment was begun with palbociclib plus letrozole, converting the disease to operability over a period of 6 mo. Surgery was performed and a p CR achieved. Of note, during treatment the patient experienced a very uncommon toxicity characterized by burning tongue and glossodynia associated with dysgeusia, paresthesia, dysesthesia, and xerostomia. A reduction in the dose of palbociclib did not provide relief and treatment with the inhibitor was thus discontinued, resolving the tongue symptoms. Laboratory exams were unremarkable. Given that this was a late relapse, the tumor was classified asendocrine-sensitive, a condition associated with high sensitivity to palbociclib.CONCLUSION This case highlights the potential of the cyclin-dependent kinase 4/6 inhibitor plus ET combination to achieve pCR in locoregional relapse of BC, enabling surgical resection of a lesion initially considered inoperable.

CDK4/6抑制剂治疗HR+/HER2-晚期乳腺癌的效果及安全性研究

目的:探讨阿贝西利联合内分泌药物治疗在激素受体阳性/人类表皮生长因子受体2阴性(hormone receptor positive/human epidermal growth factor receptor-2 negative,HR+/HER2-)晚期乳腺癌患者中的临床疗效及不良反应。方法:回顾性分析2021年2月—2022年9月在南通大学附属肿瘤医院接受阿贝西利联合内分泌治疗的70例HR+/HER2-晚期乳腺癌患者的临床病理资料。单因素及多因素Cox比例风险模型分析影响患者无进展生存期(progression-free survival,PFS)的独立预后因素,总结治疗中的不良反应。结果:70例HR+/HER2-晚期乳腺癌中接受阿贝西利治疗>6个月的患者30例(42.9%),客观缓解率为44.3%,疾病控制率为67.1%。与阿贝西利一线治疗组相比,哌柏西利转阿贝西利组PFS的HR为5.4(95%CI:1.1~26.4,P=0.04)。不良反应以白细胞减少(42.9%)和腹痛腹泻(10.0%)最常见。结论:阿贝西利联合内分泌药物治疗HR+/HER2-晚期乳腺癌患者具有良好的疗效,且不良反应可控,耐受性良好。

CDK4/6抑制剂抗肿瘤作用研究进展

细胞周期素依赖性蛋白激酶4/6(cyclin-dependent kinases 4/6,CDK4/6)与细胞周期蛋白D(cyclin D)结合,通过调节细胞G_1-S期转换,成为细胞周期调控机制的核心部分。CDK4/6-cyclin D-INK4-Rb通路的异常活化将会导致癌细胞失控性生长,该通路的异常存在于多种恶性肿瘤中,因此CDK4/6成为潜在的治疗靶点。本文对CDK4/6的作用机制,及主要几种CDK4/6抑制剂的研究进展进行综述,旨在探讨CDK4/6抑制剂在恶性肿瘤治疗中的应用前景及优化手段。

Abemaciclib, a Recent Novel FDA-Approved Small Molecule Inhibiting Cyclin-Dependant Kinase 4/6 for the Treatment of Metastatic Breast Cancer: A Mini-Review

Abemaciclib (Verzerio®) is a cell cycle inhibitor of both CDK4 and CDK6. In 2017, abemaciclib was approved by the Food and Drug Administration (FDA) and, in 2018 by the European Medicines Agency (EMA) for the treatment of postmenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−) advanced breast cancer. In this mini-review, we provide a series of information for respectively their targets and its selectivity, results on preclinical trial, clinical phase I, II and III trials, and some perspectives. We also describe the batch and flow steps used for the synthesis of this cancer drug.

Insights into the Use of CDK 4/6 Inhibitors in Patients with HR-positive Advanced or Metastatic Breast Cancer

Hormone receptor(HR)-positive breast cancer(BC)is the most common subtype of BC and some patients with such tumors experience recurrences.Endocrine-based therapy(ET)(e.g.,tamoxifen,aromatase inhibitors(AIs),and fulvestrant)that has improved outcomes in such patients represents the initial therapy for women with HR-positive/human epidermal growth factor receptor 2(HER2)-negative BC(considering no evidence of visceral crisis).However,the resistance to ET can occur in almost 50%of HR-positive BCs.In order to improve outcomes of patients with HR-positive metastatic BC,new treatment strategies are required.One such therapy is the new class of medications,cyclin-dependent kinase(CDK)4/6 inhibitors,that have improved the outcomes in such patients(both endocrine-sensitive and endocrine-resistant).This article presents evidence from the main clinical trials,which led to the approval of palbociclib,ribociclib,and abemaciclib.These three CDK 4/6 inhibitors have shown a significant improvement of the progression-free survival(PFS)in patients with HR-positive/HER2-negative metastatic BC when used in combination with selected ETs.In addition,some important patient management considerations,when choosing a particular CDK 4/6 inhibitor for an individual patient are presented.Furthermore,a need to find biomarkers for CDK 4/6 inhibitor sensitivity,efficacy,and resistance,to be able to precisely select the best patientcandidates for this treatment is highlighted.

CDK4/6 inhibitors in the treatment of hormone receptor-positive, HER2-negative advanced breast cancer

Endocrine therapy(ET)is the therapy backbone of hormone receptor(HR)-positive and human epidermal growth factor receptor 2(HER2)-negati ve advanced breast cancer.However,there are about 20%HR positive patients with no response to ET due to primary or acquired ET resistance.In this background,many agents have been studied to overcome ET resistance and of which the important agents are cyclin-dependent kinase 4/6(CDK4/6)inhibitors.The prognosis of advanced breast cancer has been improved by combing ET with CDK4/6 inhibitors.In this review,we mainly focused on the CDK4/6 inhibitors in the treatment of HR-positive,HER2-negative advanced breast cancer and discussed the action mechanisms of CDK4/6 inhibitors alone or combined with ET.We also summarized several molecular features that would predict response or resistance to CDK4/6 inhibitors.In addition,we put forward possible strategies to overcome CDK4/6 inhibitor resistance according to the latest research.

Progress of CDK4/6 inhibitors in the treatment of malignant tumors

CDK4/6 inhibitor acts on cell cycle.It can be used alone or in combination to treat lung cancer,liver cancer,pancreatic cancer and other cancers by restoring normal cell cycle,triggering anti-tumor immunity and changing the microenvironment of tumors.It has a certain therapeutic effect,and has a certain inhibitory effect on the proliferation and development of malignant tumors.The combination of other antineoplastic drugs can effectively reduce the emergence of drug resistance and synergistically enhance the clinical efficacy.This article reviews the related research results of CDK4/6 inhibitors,as well as the literature,and summarizes the mechanism and clinical application of CDK4/6 inhibitors.Cyclin dependent kinase(CDK)is a group of serine/threonine protein kinases.The chemical action of CDK on serine/threonine protein is the key to driving cell cycle.The typical biological feature of cancer is cell cycle disorder.As the engine of cell cycle,CDK and its regulators play an important role in tumorigenesis and development.In modern times,cancer has gained a deeper understanding at the level of biomolecule.For cell receptors,more and more drugs are used for key genes.The new generation of CDK4/6 inhibitors cut into the cell cycle to treat malignant tumors,prevent cells from G1 phase to S phase.They have good clinical efficacy for ER+breast cancer patients.They are also used in clinical trials of lung cancer,melanoma and other malignant tumors to treat malignant tumors.Therapy provides a new way.

Impact of Drug-Drug Interaction between CDK4/6 Inhibitors and Proton Pump Inhibitors on Survival Outcomes in the Treatment of Metastatic Breast Cancer—Real World Data from a Portuguese Center

Introduction: Proton pump inhibitors (PPi) are widely prescribed, including in patients undergoing treatment for advanced breast cancer (ABC). Due to the pharmacokinetic characteristics of the CDK4/6 inhibitor (Ci) palbociclib a drug interaction with PPi was hypothesized. It was shown in a retrospective study that this association was an independent predictive factor for worse progression-free survival (PFS). Objective: To verify the impact of concomitant administration of PPi with Ci on overall survival (OS) and PFS. Material and Methods: This is a retrospective cohort study of patients treated with Ci for HR+HER2-ABC in the period from Feb/2017 to Aug/2020. SPSS software was used for data processing. Univariate analysis was done by the Kaplan-Meier method and log-rank test, and multivariate analysis by COX regression. P-value < 0.05 was considered significant. Results: 80 patients were included. The median age at diagnosis of ABC was 56 years (25 - 75). Treatment with Ci was 1st line for ABC in 68.8%. Choice of Ci was palbociclib in 73.8% (n = 59) and ribociclib in 26.3% (n = 21). The hormone partner was a nonsteroidal aromatase inhibitor in 45.0%, and fulvestrant in 55.0% of cases. 37.5% of patients were on PPi, and 70.0% of them were during the entire treatment (23.3% omeprazole, 73.4% pantoprazole, 3.3% others). Patients taking concomitant PPi and Ci had lower OS (OS-3 years 42.6% vs. 63.4%, p = 0.254) and PFS (PFS med 15 m. vs. 21 m., p = 0.733), although with no statistically significant difference. Discussion: In the sample, there was a numerical difference, without the statistical significance in the use of PPi in the survival of patients under Ci. This difference could be more evident with a longer follow-up and a larger sample size. This study intends to alert to the growing importance of checking for drug interactions. Polymedication, advanced age and the presence of several comorbidities are real problems in patients with ABC. Conclusion: Real-world data from this center demonstrate a negative, non-statistically significant impact of PPi treatment on survival outcomes, in patients treated with Ci for HR+HER2-ABC.

A Systematic Review of Economic Evaluation of CDK4/6 Inhibitors in HR+/HER2-Advanced Breast Cancer

Objective To review the domestic and foreign economic studies on CDK4/6 inhibitors in first-line or second-line treatment of HR+/HER2-advanced breast cancer,and to analyze the main methodologies and research results.Methods Systematic literature review was used to search PubMed,EMBASE,Cochrane Library,CNKI,CBM,and Wanfang database.The incremental cost-effectiveness ratio was taken as the main outcome index,and all pharmacoeconomic evaluations with CDK4/6 inhibitors as intervention measures were included,such as Palbociclib,Ribociclib,and Abemaciclib.According to the Quality of Health Economic Studies Instrument,the quality of the included articles was evaluated,and then the included literature was analyzed.Results and Conclusion A total of 16 pharmacoeconomic evaluation studies were included,mainly from the perspective of national healthcare systems or third-party payers.Only 2 studies focused on second-line treatment,and the remaining treatment levels were first-line treatment.In terms of model structure,7 studies adopted the Markov model,6 studies adopted the PSM model,and 3 studies adopted the DES model.The basic analysis results showed that CDK4/6 inhibitor combined with endocrine regimen was not economical compared with endocrine alone regimen when the threshold was the conventional willingness to pay(WTP)value of each country.The uncertainty analysis included deterministic sensitivity analysis and probability sensitivity analysis.The included studies are all Cost-Utility Analysis with high-quality evaluation,which can provide evidence support for health-related decision-makers in decision-making.It can also provide methodological reference for the economic evaluation of other targeted drugs.

细胞周期蛋白依赖性激酶4/6抑制剂治疗激素受体阳性、人表皮生长因子受体2阴性的晚期乳腺癌的研究进展

激素受体阳性(hormone receptor positive,HR+)、人表皮生长因子受体2阴性(human epidermal growth factor receptor 2 negative,HER2−)的乳腺癌是乳腺癌中最常见的分子亚型,预后情况常取决于患者对内分泌治疗的敏感性。HR+、HER2−晚期乳腺癌多已对内分泌治疗药物耐药,而此往往会致患者生存期缩短、生命质量下降等不良结局,故临床上亟需有新的治疗策略/药物。近年来,一些新型口服靶向药物细胞周期蛋白依赖性激酶(cyclin-dependent kinase,CDK)4/6抑制剂陆续获准上市,它们因能为HR^(+)、HER2^(−)晚期乳腺癌患者提供显著的生存益处且安全性良好,成为该类患者的重要有效治疗选择之一。本文就CDK4/6抑制剂的作用机制、有效性、安全性和药物经济学研究进展作一概要介绍和对比分析。

CDK4/6抑制剂耐药机制的研究进展

细胞周期依赖性激酶4/6(cyclin-dependent kinase 4/6,CDK4/6)抑制剂能作用于过度活化的CDK4/6,恢复正常细胞周期,并通过触发免疫,改变肿瘤微环境等发挥抗肿瘤作用。目前,CDK4/6抑制剂的问世极大地改善了激素受体阳性(hormone receptor-positive,HR^(+))、人表皮生长因子受体2阴性(human epidermal growth factor receptor 2-negative,HER2^(-))晚期乳腺癌患者的预后,使无进展生存期(progression-free-survival,PFS)增加近一倍,且不良反应可控。尽管如此,这类患者最终仍会因CDK4/6抑制剂耐药而出现疾病进展。CDK4/6抑制剂的耐药机制十分复杂,尚未完全明确。预测其早期耐药或治疗敏感的生物标记物也有待确定。本文对CDK4/6抑制剂治疗的作用机制及耐药机制进行梳理和总结,并对疾病进展后的治疗策略作简要讨论。

靶向抑制CDK4/6的肿瘤治疗基础研究与临床应用进展

周期蛋白依赖性激酶4/6(cyclin-dependent kinase 4/6,CDK4/6)是一类丝氨酸/苏氨酸激酶,通过与细胞周期蛋白D(cyclin D)结合,调节视网膜母细胞瘤蛋白(Rb)的磷酸化状态,Rb磷酸化后与E2F转录因子分离,释放的E2F可以自由激活一系列基因表达,参与DNA复制和细胞分裂,从而介导细胞G 1/S期转换,影响细胞周期的进程。近年研究发现CDK4/6在多种肿瘤发生和发展过程中起着核心作用,已成为临床多种肿瘤治疗的重要分子靶点。本文将对CDK4/6与肿瘤的关系以及CDK4/6抑制剂临床应用的最新研究进展做一综述。

CDK4/6抑制剂治疗HR阳性和HER2阴性晚期乳腺癌的作用机制研究进展

内分泌疗法是晚期乳腺癌的主要治疗方案,具有较好的疗效和安全性,尤其对于激素受体(HR)阳性和人表皮生长因子受体2(HER2)阴性的晚期乳腺癌患者。内分泌治疗在很大程度上提高了乳腺癌综合治疗的效果。细胞周期蛋白依赖性激酶(CDK)抑制剂作为主要的内分泌治疗药物,具有调控晚期乳腺癌患者的细胞周期、阻断肿瘤细胞增殖的作用。因此,CDK4/6抑制剂有望成为未来有效治疗HR阳性和HER2阴性晚期乳腺癌的新型药物,而研究分析CDK4/6抑制剂治疗HR阳性和HER2阴性晚期乳腺癌的作用机制可以为临床治疗提供参考。

基于FAERS数据库的CDK4/6抑制剂发生血栓栓塞不良事件的信号挖掘研究

目的基于美国食品药品管理局(FDA)不良事件报告系统(FAERS)数据库,挖掘细胞周期蛋白依赖激酶4/6抑制剂发生血栓栓塞相关不良事件的信号,为临床安全用药提供参考。方法采用报告比值比法(ROR法)和综合标准法(MHRA法)挖掘FAERS数据库2019年第1季度—2021年第3季度共计11个季度的报告数据。结果挖掘到与CDK4/6抑制剂相关的血栓不良事件的报告627份,形成信号的血栓不良事件有7种,累及“血管与淋巴管类疾病”和“呼吸系统、胸及纵膈疾病”两个系统,7种不良事件以血栓形成和肺栓塞报告例数居多,其造成的死亡和危及生命的结局占比也最高。结论就目前的研究,支持乳腺癌患者在使用CDK4/6抑制剂时对于血栓栓塞不良事件的风险担忧,临床医生在使用CDK4/6抑制剂前,需充分评估患者发生血栓的风险因素(包括年龄、肥胖及血栓既往史等),并且提醒患者关注与血栓相关的临床症状,一旦发现,应及时就医。

CDK4/6抑制剂所致药物不良反应文献分析及思考

目的分析CDK4/6抑制剂在临床应用中所致不良反应(ADR)的特点,为临床安全用药提供参考。方法检索维普、中国知网、万方、Web of Science、PubMed等数据库中关于CDK4/6抑制剂致ADRs的文献并进行分析。结果CDK4/6抑制剂致ADRs的个案报道共34例;患者平均年龄约63.5岁,ADRs多发生在用药4个月内(29例,85.29%);CDK4/6抑制剂致ADRs主要以皮肤及其附件损害(14例,41.18%)、呼吸系统损害(6例,17.65%)、肝胆系统损害(4例,11.76%)为主;经停药和/或对症治疗后达到症状好转或治愈的有31例;3例最终死亡。结论临床使用CDK4/6抑制剂时应加强用药监测,开展多学科患者管理,而CDK4/6抑制剂的ADR发生机制尚需进一步研究。

CDK4/6抑制剂联合内分泌药物治疗HR阳性/HER2阴性乳腺癌疗效与安全性的Meta分析

目的 评价4种周期蛋白依赖性激酶4/6(CDK4/6)抑制剂(达尔西利、阿贝西利、瑞波西利、哌柏西利)联合内分泌药物治疗激素受体(HR)阳性/人表皮生长因子受体2(HER2)阴性乳腺癌的疗效和安全性。方法 计算机检索PubMed、the Cochrane Library、Web of Science、Embase、中国知网、万方数据、维普网,收集CDK4/6抑制剂联合内分泌药物(试验组)对比单用内分泌药物或联用安慰剂(对照组)的随机对照试验(RCT),检索时限为建库至2023年4月。筛选文献、数据提取和质量评价后,采用RevMan 5.4.1软件进行Meta分析。结果 共纳入22篇文献,涉及15项RCT,合计18 574例患者。Meta分析结果显示,试验组患者的无进展生存期[HR=0.77,95%CI(0.74,0.79),P<0.000 01]、总生存期[HR=0.91,95%CI(0.87,0.94),P<0.000 01]、客观缓解率[OR=1.71,95%CI(1.51,1.93),P<0.000 01]、临床获益率[OR=1.73,95%CI(1.52,1.95),P<0.000 01]均显著优于对照组。试验组患者的≥3级不良反应[OR=10.28,95%CI(6.97,15.17),P<0.000 01]、中性粒细胞减少[OR=65.09,95%CI(36.43,116.31),P<0.000 01]、白细胞减少[OR=22.90,95%CI(15.40,34.04),P<0.000 01]、贫血[OR=5.71,95%CI(4.51,7.22),P<0.000 01]、腹泻[OR=3.00,95%CI(1.19,7.51),P<0.05]、恶心[OR=1.99,95%CI(1.52,2.60),P<0.00001]发生率均显著高于对照组。结论CDK4/6抑制剂联合内分泌药物治疗HR阳性/HER2阴性乳腺癌的疗效显著,不良反应发生率较高,尤其是血液毒性反应。