中国药业2025，Vol.34Issue(10)：后插2-后插7,6.DOI:10.3969/j.issn.1006-4931.2025.10.029
AKT抑制剂capivasertib治疗乳腺癌研究进展
Research Progress of AKT Inhibitor Capivasertib in the Theatment of Breast Cancer
摘要
Abstract
Objective To provide a reference for the treatment of breast cancer with protein kinase B(AKT)inhibitor capivasertib.Methods Relevant literature performed in Web of Science,GeenMedical,PubMed,ClinicalTrials,CNKI,Wanfang database from 2010 to 2024 were searched by using computer.The mechanism of action,pharmacokinetics,and pharmacodynamics of capivasertib in breast cancer treatment were analyzed,and the safety of its clinical application was summarized.Results The main mechanism of capivasertib is to inhibit all AKT subtypes,prevent substrate phosphorylation caused by AKT,and block phosphatidylinositol 3-kinase(PI3K)/AKT signaling,thereby inhibiting tumor growth.In the dose range of 80-800 mg,the exposure of capivasertib is positively correlated with the dose.After the first oral administration of 80 mg,the time to reach the median maximum plasma concentration is 2 hours.Each time 480 mg,twice daily,4 days on/3 days off every week(4/7 dosing regimen)is suitable for long-term use.The dosage form and food metabolism have no significant effect on capivasertib,and capivasertib can be excreted through feces and urine.Phase Ⅰ drug clinical trials showed that compared with capivasertib monotherapy,the objective response rate(ORR)of combined fulvestrant treatment was higher(36%vs.20%).Phase Ⅱ drug clinical trials showed that capivasertib combined with fulvestrant could significantly prolong the overall survival and progression-free survival(PFS)of patients.Phase Ⅲdrug clinical trials showed that in patients with hormone receptor(HR)positive/human epidermal growth factor receptor 2(HER2)negative advanced breast cancer with AKT mutations,capivasertib combined with fulvestrant treatment significantly prolonged PFS and improved ORR compared with fulvestrant monotherapy.Phase Ⅰ,Ⅱ and Ⅲ drug clinical trials showed that the common adverse reactions of capivasertib in the treatment of patients with advanced breast cancer were diarrhea,nausea and rash,which could be tolerated by patients.Conclusion Capivasertib has shown good prospects in the treatment of HR positive/HER2 negative breast cancer.It can significantly improve the PFS of patients by inhibiting the AKT pathway and combined with endocrine therapy.关键词
capivasertib/乳腺癌/蛋白激酶B抑制剂/细胞周期蛋白依赖性激酶4/细胞周期蛋白依赖性激酶6Key words
capivasertib/breast cancer/protein kinase B inhibitor/cyclin-dependent kinase 4/cyclin-dependent kinase 6分类
药学引用本文复制引用
廖强,杨林,徐晓菲,韩娟,程凯..AKT抑制剂capivasertib治疗乳腺癌研究进展[J].中国药业,2025,34(10):后插2-后插7,6.基金项目
四川省医学重点学科(实验室)及重点专项立项建设项目[川卫发[2019]30号]. （实验室）
