Acceptability of Drugs in the Treatment of Unresectable/Metastatic BRAF V600-Mutant Melanoma: A Systematic Review and Network Meta-Analysis.
Acceptability of Drugs in the Treatment of Unresectable/Metastatic BRAF V600-Mutant Melanoma: A Systematic Review and Network Meta-Analysis.
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DOI：
10.3389/fonc.2022.865656
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发表时间：
2022
影响因子：
4.7
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中科院分区：
文献类型：
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尽管许多新方案已经进入了不可切除/转移性BRAF v600突变黑色素瘤的治疗范式，但在安全性方面仍然缺乏正面比较。我们进行了一项网络荟萃分析，以比较不同治疗方法的不良事件（ae）风险，并为患者提供可接受性排名。在Embase、PubMed、世卫组织国际临床试验注册平台和Clinical Trials.gov上进行了系统的文献综述，时间框架从数据库建立到2021年12月24日。我们根据合并风险比（rr）和95%可信区间（95% CrI）检索了任意级别ae累积发生率的证据，即1-5级ae（无论严重程度）和严重ae。纳入了12篇出版物和13种治疗方法，共纳入5803例患者。对于任何级别的ae，达非尼联合曲美替尼的可接受性优于维穆非尼联合柯比美替尼（RR: 0.94; Crl: 0.89, 0.98）。此外，纳武单抗联合伊匹单抗比单药伊匹单抗（RR: 0.90; Crl: 0.83, 0.96）或纳武单抗（RR: 0.90; Crl: 0.84, 0.97）增加了任何级别的ae。对于严重ae， dabrafenib的可接受性优于单药vemurafenib （RR: 0.66; Crl: 0.50, 0.87）或encorafenib （RR: 0.64; Crl: 0.43, 0.94）。此外，伊匹单抗（SUCRA: 0.87）在任何级别ae的可接受性中排名第一，纳武单抗（SUCRA: 0.95）在严重ae的可接受性中排名第一。vemurafenib与cobimetinib联合用药（SUCRA: 0.66）的排名优于encorafenib与binimetinib联合用药（SUCRA: 0.39）和vemurafenib与cobimetinib联合用药（SUCRA: 0.18）。我们确定了BRAF v600突变黑色素瘤患者AE风险最低的治疗方案。一般来说，免疫疗法（易普利姆单抗或纳沃单抗）比大多数靶向治疗具有更好的可接受性，而三联疗法的可接受性最差。单药达非尼可作为单药治疗的首选，达非尼联合曲美替尼是首选的联合治疗。总的来说，与单一药物相比，免疫治疗药物联合使用会增加任何级别和严重的ae，而靶向治疗药物的情况不能简单地一概而论。因此，这些信息可以促进循证决策，并支持在临床实践中优化治疗和结果。
Although many novel regimens have entered the treatment paradigm for unresectable/metastatic BRAF V600-mutant melanoma, there is still a lack of head-to-head comparison in terms of security. We conducted a network meta-analysis to compare the risk of adverse events (AEs) across different treatments and to provide an acceptability ranking for patients. A systematic literature review was conducted in Embase, PubMed, WHO International Clinical Trials Registry Platform, and Clinical Trials.gov with a time frame from database inception to December 24, 2021. We retrieved evidence on the cumulative incidence of any-grade AEs means grades 1-5 AEs (regardless of severity) and severe AEs based on the pooled risk ratios (RRs) and 95% credible intervals (95% CrI). Twelve publications and thirteen treatments enrolling 5,803 patients were included. For any-grade AEs, the acceptability of combined dabrafenib and trametinib is superior to the combination of vemurafenib and cobimetinib (RR: 0.94; Crl: 0.89, 0.98). Furthermore, nivolumab combined with ipilimumab increases any-grade AEs than single-agent ipilimumab (RR: 0.90; Crl: 0.83, 0.96) or nivolumab (RR: 0.90; Crl: 0.84, 0.97). For severe AEs, dabrafenib has the best acceptability than single-agent vemurafenib (RR: 0.66; Crl: 0.50, 0.87) or encorafenib (RR: 0.64; Crl: 0.43, 0.94). In addition, ipilimumab (SUCRA: 0.87) ranks first in the acceptability for any-grade AEs, and nivolumab (SUCRA: 0.95) ranks first in the acceptability for severe AEs. The ranking of the combination of vemurafenib and cobimetinib (SUCRA: 0.66) is superior to encorafenib in combination with binimetinib (SUCRA: 0.39) and combination of vemurafenib and cobimetinib (SUCRA: 0.18). We identified the lowest AE risk treatment options for BRAF V600-mutant melanoma patients. In general, immunotherapy (ipilimumab or nivolumab) has better acceptability than most targeted therapies, and triplet therapies are related with the worst acceptability. Moreover, single-agent dabrafenib can be used as the first choice in monotherapy, and the combination of dabrafenib and trametinib is the preferred combination therapy. Overall, the combination of immunotherapy drugs increases any-grade and severe AEs than a single agent, whereas the condition of targeted therapy drugs cannot be simply generalized. Therefore, this information can facilitate evidence-based decision-making and support optimizing treatment and outcomes in clinical practice.
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影响因子：
10.9
作者：
Ferrucci PF;Di Giacomo AM;Del Vecchio M;Atkinson V;Schmidt H;Schachter J;Queirolo P;Long GV;Stephens R;Svane IM;Lotem M;Abu-Amna M;Gasal E;Ghori R;Diede SJ;Croydon ES;Ribas A;Ascierto PA;KEYNOTE-022 international team
通讯作者：
KEYNOTE-022 international team
影响因子：
4
作者：
da Silveira Nogueira Lima JP;Georgieva M;Haaland B;de Lima Lopes G
通讯作者：
de Lima Lopes G
影响因子：
8.4
作者：
Ascierto, Paolo A.;Dummer, Reinhard;Robert, Caroline
通讯作者：
Robert, Caroline
影响因子：
2.2
作者：
Edlundh-Rose, Esther;Egyhazi, Suzanne;Lundeberg, Joakim
通讯作者：
Lundeberg, Joakim
影响因子：
45.3
作者：
Ascierto, Paolo A.;Minor, David;Trefzer, Uwe
通讯作者：
Trefzer, Uwe