4种CDK4/6抑制剂用于晚期乳腺癌的安全性网状Meta分析★

Safety of four CDK4/6 inhibitors in advanced breast cancer: a network Meta-analysis★

摘要:

目的 利用网状Meta分析方法对周期蛋白依赖性激酶4/6（CDK4/6）抑制剂在晚期乳腺癌中的安全性进行分析。方法 在中英文数据库中检索阿贝西利、哌柏西利、瑞波西利、达尔西利治疗晚期或转移性乳腺癌的临床研究，检索时间截至2023年6月12日。使用ADDIS软件进行网状Meta分析，探索阿贝西利、哌柏西利、瑞波西利、达尔西利联合内分泌治疗之间的安全性差异，并对该类药物的血液毒性进行对比分析。结果 共纳入14项研究，共5种干预措施，6 513例患者。对严重不良事件（SAE）进行分析，SAE发生率从高到低依次为阿贝西利+内分泌治疗、瑞波西利+内分泌治疗、达尔西利+内分泌治疗、哌柏西利+内分泌治疗、内分泌治疗。血液学毒性方面，中性粒细胞减少发生率从高到低依次为达尔西利+内分泌治疗、哌柏西利+内分泌治疗、瑞波西利+内分泌治疗、阿贝西利+内分泌治疗、内分泌治疗；白细胞减少发生率从高到低依次为达尔西利+内分泌治疗、哌柏西利+内分泌治疗、阿贝西利+内分泌治疗、瑞波西利+内分泌治疗、内分泌治疗；贫血发生率从高到低依次为达尔西利+内分泌治疗、阿贝西利+内分泌治疗、哌柏西利+内分泌治疗、瑞波西利+内分泌治疗、内分泌治疗；血小板减少发生率从高到低依次为哌柏西利+内分泌治疗、达尔西利+内分泌治疗、阿贝西利+内分泌治疗、瑞波西利+内分泌治疗、内分泌治疗。结论 阿贝西利+内分泌治疗的SAE发生率高于其他CDK4/6抑制剂，达尔西利+内分泌治疗的中性粒细胞减少、白细胞减少、贫血发生率高于其他CDK4/6抑制剂，哌柏西利+内分泌治疗的血小板减少发生率高于其他CDK4/6抑制剂，单纯内分泌治疗的SAE和血液毒性发生率最低，但上述结果还需更多高质量的头对头随机对照试验验证。临床医生和药师应更有针对地使用CDK4/6抑制剂，并及时对患者的不良反应做出积极、有效的应对，以最大限度提高药物疗效，降低患者用药风险。

Abstract:

Objective To compare and analyze the safety of cyclin-dependent kinase 4/6 inhibitors in advanced breast cancer by using network Meta-analysis.Methods Abemaciclib, palbociclib, ribociclib and dalpiciclib were searched in Chinese and English databases for clinical research on advanced or metastatic breast cancer until June 12, 2023. Network Meta-analysis was carried out with ADDIS software to explore the safety differences among the combined endocrine therapy of abemaciclib, palbociclib, ribociclib and dalpiciclib, and the blood toxicity of these drugs was compared and analyzed.Results A total of 14 studies, 5 interventions and 6 513 patients were included. The serious adverse events index was analyzed, and the ranking chart showed that the sequence of SAE occurrence probability of each intervention measure from high to low was abemaciclib+endocrine therapy (ET), ribociclib+ET, dalpiciclib+ET, palbociclib+ET, and ET. The order of neutropenia occurrence probability of each intervention measure from high to low was dalpiciclib+ET, palbociclib+ET, ribociclib+ET, abemaciclib+ET, and ET. The order of the occurrence probability of leukopenia of each intervention measure from high to low was dalpiciclib+ET, palbociclib+ET, abemaciclib+ET, ribociclib+ET, and ET. The order of the incidence probability of anemia in each intervention measure from high to low was dalpiciclib+ET, abemaciclib+ET, palbociclib+ET, ribociclib+ET, and ET. The order of the incidence probability of thrombocytopenia of each intervention measure from high to low was palbociclib+ET, dalpiciclib+ET, abemaciclib+ET, ribociclib+ET, and ET.Conclusion The incidence probability of SAE and thrombocytopenia in abemaciclib+ET was higher than that in other CDK4/6 inhibitors.The incidence probability of neutropenia, leukopenia and anemia of dalpiciclib+ET was higher than that of other CDK4/6 inhibitors. The incidence probability of thrombocytopenia of palbociclib+ET was higher than that of other CDK4/6 inhibitors. ET alone had the lowest incidence probability of SAE and blood toxicity. The results need to be verified by more high-quality randomized controlled trials of head-to-head comparison. Clinicians and pharmacists should use CDK4/6 inhibitors more specifically, and respond positively and effectively to the adverse reactions in time, so as to maximize the efficacy of drugs and reduce the risk of patients' medication.