Abstract：
The objective of this study was to estimate the relative efficacy and safety of targeted therapies for the treatment of metastatic melanoma using a network meta-analysis (NMA).
A systematic literature review (SLR) identified studies in Medline, Embase and Cochrane published until November 2020. Screening used prespecified eligibility criteria. Following a transitivity assessment across included studies, Bayesian NMA was conducted.
A total of 43 publications reporting 15 targeted therapy trials and 42 reporting 18 immunotherapy trials were retained from the SLR and considered for the NMA. Due to substantial between-study heterogeneity with immunotherapy trials, the analysis considered a network restricted to targeted therapies. Among combination therapies, encorafenib + binimetinib was superior to dabrafenib + trametinib for overall response rate (OR = 1.86; 95 % credible interval [CrI] 1.10, 3.17), superior to vemurafenib + cobimetinib with fewer serious adverse events (SAEs) (OR = 0.51; 95 % CrI 0.29, 0.91) and fewer discontinuations due to AEs (OR = 0.45; 95 % CrI 0.21, 0.96), and superior to atezolizumab + vemurafenib + cobimetinib with fewer SAEs (OR = 0.41; 95 % CrI 0.21, 0.82). Atezolizumab + vemurafenib + cobimetinib and encorafenib + binimetinib were generally comparable for efficacy endpoints. Among double combination therapies, encorafenib + binimetinib showed high probabilities of being better for all efficacy and safety endpoints.
This NMA confirms that combination therapies are more efficacious than monotherapies. Encorafenib + binimetinib has a favourable efficacy profile compared to other double combination therapies and a favourable safety profile compared to both double and triple combination therapies.
A systematic literature review (SLR) identified studies in Medline, Embase and Cochrane published until November 2020. Screening used prespecified eligibility criteria. Following a transitivity assessment across included studies, Bayesian NMA was conducted.
A total of 43 publications reporting 15 targeted therapy trials and 42 reporting 18 immunotherapy trials were retained from the SLR and considered for the NMA. Due to substantial between-study heterogeneity with immunotherapy trials, the analysis considered a network restricted to targeted therapies. Among combination therapies, encorafenib + binimetinib was superior to dabrafenib + trametinib for overall response rate (OR = 1.86; 95 % credible interval [CrI] 1.10, 3.17), superior to vemurafenib + cobimetinib with fewer serious adverse events (SAEs) (OR = 0.51; 95 % CrI 0.29, 0.91) and fewer discontinuations due to AEs (OR = 0.45; 95 % CrI 0.21, 0.96), and superior to atezolizumab + vemurafenib + cobimetinib with fewer SAEs (OR = 0.41; 95 % CrI 0.21, 0.82). Atezolizumab + vemurafenib + cobimetinib and encorafenib + binimetinib were generally comparable for efficacy endpoints. Among double combination therapies, encorafenib + binimetinib showed high probabilities of being better for all efficacy and safety endpoints.
This NMA confirms that combination therapies are more efficacious than monotherapies. Encorafenib + binimetinib has a favourable efficacy profile compared to other double combination therapies and a favourable safety profile compared to both double and triple combination therapies.
摘要：
这项研究的目的是使用网络荟萃分析（NMA）评估靶向治疗转移性黑色素瘤的相对疗效和安全性。
Medline的系统文献综述(SLR)确定的研究，Embase和Cochrane发布至2020年11月。筛选使用预先指定的合格标准。在纳入研究的传递性评估之后，进行贝叶斯NMA。
从SLR中保留了43篇报告15个靶向治疗试验和42篇报告18个免疫治疗试验的出版物，并考虑用于NMA。由于免疫治疗试验的研究之间的实质性异质性，分析认为网络仅限于靶向治疗.在联合疗法中，恩科非尼+比尼美替尼的总缓解率优于达拉非尼+曲美替尼(OR=1.86;95%可信区间[CrI]1.10,3.17)，优于vemurafenib+cobimetinib，具有更少的严重不良事件（SAE）（OR=0.51;95％CrI0.29，0.91）和更少的因AE（OR=0.45;95％CrI0.21，0.96），优于阿特珠单抗+维罗非尼+考比替尼,SAE较少(OR=0.41;95%CrI0.21,0.82).阿替珠单抗+维罗非尼+考比替尼和恩可拉非尼+比米替尼在疗效终点方面通常相当。在双重联合疗法中，恩可拉非尼+比米替尼在所有疗效和安全性终点均表现出更好的可能性.
该NMA证实组合疗法比单一疗法更有效。恩科非尼+比尼美替尼与其他双重组合疗法相比具有有利的疗效特征,并且与双重和三重组合疗法相比具有有利的安全性特征。
Medline的系统文献综述(SLR)确定的研究，Embase和Cochrane发布至2020年11月。筛选使用预先指定的合格标准。在纳入研究的传递性评估之后，进行贝叶斯NMA。
从SLR中保留了43篇报告15个靶向治疗试验和42篇报告18个免疫治疗试验的出版物，并考虑用于NMA。由于免疫治疗试验的研究之间的实质性异质性，分析认为网络仅限于靶向治疗.在联合疗法中，恩科非尼+比尼美替尼的总缓解率优于达拉非尼+曲美替尼(OR=1.86;95%可信区间[CrI]1.10,3.17)，优于vemurafenib+cobimetinib，具有更少的严重不良事件（SAE）（OR=0.51;95％CrI0.29，0.91）和更少的因AE（OR=0.45;95％CrI0.21，0.96），优于阿特珠单抗+维罗非尼+考比替尼,SAE较少(OR=0.41;95%CrI0.21,0.82).阿替珠单抗+维罗非尼+考比替尼和恩可拉非尼+比米替尼在疗效终点方面通常相当。在双重联合疗法中，恩可拉非尼+比米替尼在所有疗效和安全性终点均表现出更好的可能性.
该NMA证实组合疗法比单一疗法更有效。恩科非尼+比尼美替尼与其他双重组合疗法相比具有有利的疗效特征,并且与双重和三重组合疗法相比具有有利的安全性特征。
