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.
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。