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重庆大学附属肿瘤医院药学部,重庆 400030
主管药师,硕士。研究方向:临床药学。电话:023-65317205。E-mail:songhaichiuk123@163.com
副主任药师,硕士。研究方向:医院药学、药事管理。电话:023-65317205。E-mail:wanyichen_cquch@163.com
纸质出版日期:2024-01-15,
收稿日期:2023-05-09,
修回日期:2023-10-10,
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宋海驰,唐宗伟,陈万一.转移性激素敏感性前列腺癌药物治疗方案的网状Meta分析 Δ[J].中国药房,2024,35(01):84-89.
SONG Haichi,TANG Zongwei,CHEN Wanyi.Pharmacotherapy plan for metastatic hormone-sensitive prostate cancer:a network meta-analysis[J].ZHONGGUO YAOFANG,2024,35(01):84-89.
宋海驰,唐宗伟,陈万一.转移性激素敏感性前列腺癌药物治疗方案的网状Meta分析 Δ[J].中国药房,2024,35(01):84-89. DOI: 10.6039/j.issn.1001-0408.2024.01.15.
SONG Haichi,TANG Zongwei,CHEN Wanyi.Pharmacotherapy plan for metastatic hormone-sensitive prostate cancer:a network meta-analysis[J].ZHONGGUO YAOFANG,2024,35(01):84-89. DOI: 10.6039/j.issn.1001-0408.2024.01.15.
目的
2
确定转移性激素敏感性前列腺癌(mHSPC)的最佳治疗方案,为临床决策提供依据。
方法
2
系统检索Medline、Embase、BIOSIS preview、the Cochrane Library和ClinicalTrials.gov数据库,收集关于mHSPC药物治疗,且疗效结局为总生存期(OS)和放射学无进展生存期(rPFS)、安全性结局为严重不良事件(SAEs)发生率的随机对照试验。检索时限为建库至2022年3月。由2名研究人员独立筛选文献、提取资料并评价纳入研究的偏倚风险后,进行贝叶斯网状Meta分析。
结果
2
最终纳入8项研究,共计9 437例患者,比较了7种治疗方案[醋酸阿比特龙、阿帕他胺、达罗他胺+多西他赛、多西他赛、恩杂鲁胺、标准非甾体抗雄激素(SNA)分别联合雄激素剥夺疗法(ADT)和单用ADT]的有效性和安全性。疗效指标中,能使患者OS获益最多的方案(除ADT+SNA外)是ADT+达罗他胺+多西他赛(HR=0.54,95%CI为0.44~0.66),随后为ADT+醋酸阿比特龙(HR=0.64,95%CI为0.57~0.71)、阿帕他胺(HR=0.65,95%CI为0.53~0.79)或恩杂鲁胺(HR=0.66,95%CI为0.53~0.82),最后是ADT+多西他赛(HR=0.79,95%CI为0.71~0.88)。能使患者rPFS获益最多的方案(除ADT+SNA外)为ADT+恩杂鲁胺(HR=0.39,95%CI为0.30~0.50),随后是ADT+阿帕他胺(HR=0.48,95%CI为0.39~0.60)、醋酸阿比特龙(HR=0.57,95%CI为0.51~0.64)或多西他赛(HR=0.62,95%CI为0.56~0.69);肿瘤负荷亚组分析的结果相同。在安全性方面,ADT+达罗他胺+多西他赛(OR=25.86,95%CI为14.08~51.33)和ADT+多西他赛(OR=23.35,95%CI为13.26~44.81)与SAEs发生率显著升高相关,ADT+醋酸阿比特龙(OR=1.42,95%CI为1.10~1.82)的SAEs发生率稍有增高,其他治疗方案的SAEs发生率无明显差异。
结论
2
与仅行ADT相比,ADT+达罗他胺+多西他赛三联疗法的OS获益最多,但其SAEs发生率大幅增高;与ADT+多西他赛相比,ADT+醋酸阿比特龙、阿帕他胺或恩杂鲁胺具有更多的OS获益。ADT+恩杂鲁胺在不提高患者SAEs发生率的前提下,提供了较多的rPFS获益。
OBJECTIVE
2
To determine the optimal therapeutic plan for metastatic hormone-sensitive prostate cancer (mHSPC), and to provide reference for clinical decision-making.
METHODS
2
Retrieved from Medline, Embase, BIOSIS preview, the Cochrane Library and ClinicalTrials.gov systematically, randomized controlled trials about mHSPC therapy, with overall survival (OS) and radiographic progression-free survival (rPFS) as efficacy outcomes and the incidence of serious adverse events (SAEs) as safety outcome, were collected during the inception-Mar. 2022. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias for the included study before conducting a Bayesian network meta-analysis.
RESULTS
2
Eight studies with 9 437 patients were finally included. The effectiveness and safety of 7 therapy plans were compared [abiraterone acetate, apalutamide, darolutamide+docetaxel, docetaxel, enzalutamide, standard non-steroidal antiandrogen (SNA) in addition to ADT, and ADT alone]. In terms of efficacy index, the most beneficial regimen (except for ADT+SNA) for OS was ADT+darolutamide+docetaxel (HR=0.54, 95%CI of 0.44-0.66), followed by ADT+abiraterone acetate (HR=0.64,95%CI of 0.57-0.71), apalutamide (HR=0.65, 95%CI of 0.53-0.79), enzalutamide (HR=0.66, 95%CI of 0.53-0.82); the least beneficial regimen for OS was ADT+docetaxel (HR=0.79, 95%CI of 0.71-0.88). The most beneficial regimen (except for ADT+SNA) for rPFS was ADT+enzalutamide (HR=0.39, 95%CI of 0.30-0.50), followed by ADT+apalutamide (HR=0.48, 95%CI of 0.39-0.60), abiraterone acetate (HR=0.57, 95%CI of 0.51-0.64), docetaxel (HR=0.62, 95%CI of 0.56-0.69). The results of the tumor-loading subgroup analysis were the same. In terms of safety, ADT+darolutamide+docetaxel (OR=25.86, 95%CI of 14.08-51.33), and ADT+docetaxel (OR=23.35, 95%CI of 13.26-44.81) were associated with markedly increased SAEs; the incidence of SAEs caused by ADT+abiraterone acetate (OR=1.42, 95%CI of 1.10-1.82) was slightly increased, and those of other therapy plans had no significant difference.
CONCLUSIONS
2
Compared with ADT alone, ADT+darolutamide+docetaxel may provide the most significant OS benefit, but the incidence of SAEs is increased greatly; compared with ADT+docetaxel, ADT+abiraterone acetate, apalutamide or enzalutamide provide more OS benefits. ADT+enzalutamide provide optimal rPFS benefits with no increased SAEs.
转移性激素敏感性前列腺癌雄激素剥夺疗法药物治疗方案网状Meta分析
androgen deprivation therapypharmacotherapy plannetwork meta-analysis
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