Hong Ling, Huang Ping, Zheng Xiaochun, Ye Xiaolan, Zhao Hongying, Wang Jianwei, Shao Yanfei
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, China.
Front Oncol. 2022 Apr 21;12:865656. doi: 10.3389/fonc.2022.865656. eCollection 2022.
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.
尽管许多新的治疗方案已进入不可切除/转移性BRAF V600突变黑色素瘤的治疗模式，但在安全性方面仍缺乏直接比较。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、世界卫生组织国际临床试验注册平台和ClinicalTrials.gov上进行了系统的文献综述，时间范围从数据库建立到2021年12月24日。我们根据汇总风险比（RR）和95%可信区间（95%CrI）检索了关于任何级别的AE（即1-5级AE，无论严重程度如何）和严重AE累积发生率的证据。
纳入了12篇出版物和13种治疗方法，共5803例患者。对于任何级别的AE，达拉非尼和曲美替尼联合使用的可接受性优于维莫非尼和考比替尼联合使用（RR：0.94；Crl：0.89，0.98）。此外，纳武单抗联合伊匹木单抗比单药伊匹木单抗（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，达拉非尼的可接受性优于单药维莫非尼（RR：0.66；Crl：0.50，0.87）或恩考芬尼（RR：0.64；Crl：0.43，0.94）。此外，伊匹木单抗（SUCRA：0.87）在任何级别的AE可接受性中排名第一，纳武单抗（SUCRA：0.95）在严重AE可接受性中排名第一。维莫非尼和考比替尼联合使用的排名（SUCRA：0.66）优于恩考芬尼与比美替尼联合使用（SUCRA：0.39）以及维莫非尼和考比替尼联合使用（SUCRA：0.18）。
我们确定了BRAF V600突变黑色素瘤患者AE风险最低的治疗选择。总体而言，免疫疗法（伊匹木单抗或纳武单抗）比大多数靶向疗法具有更好的可接受性，三联疗法的可接受性最差。此外，单药达拉非尼可作为单药治疗的首选，达拉非尼和曲美替尼联合使用是首选的联合治疗方法。总体而言，免疫治疗药物联合使用比单药增加了任何级别和严重AE的发生，而靶向治疗药物的情况不能简单一概而论。因此，这些信息有助于基于证据的决策，并支持在临床实践中优化治疗和改善结局。
