Li Yan, Liang Xueyan, Li Huijuan, Chen Xiaoyu
Department of Pharmacy, Guangxi Academy of Medical Sciences and the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People's Republic of China.
Phase 1 Clinical Trial Laboratory, Guangxi Academy of Medical Sciences and the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People's Republic of China.
Int Immunopharmacol. 2023 Feb;115:109657. doi: 10.1016/j.intimp.2022.109657. Epub 2023 Jan 4.
Immune checkpoint inhibitors (ICIs) have entered the treatment paradigm for unresectable advanced melanoma, but there is a lack of evidence regarding its relative efficacy and safety. This study aim to compare the efficacy and safety of ICIs in patients with advanced unresectable melanoma.
Studies included randomized clinical trials (RCTs) that compared ICIs, or combination therapy of ICIs, or with chemotherapy drugs, different ICIs, or one of the ICIs at different dosing schedules. Random-effects models of Bayesian network meta-analysis were performed following the PRISMA reporting guideline. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included objective response rate (ORR), disease control rate (DCR), and adverse events.
CRD42021229086.
Twenty-four RCTs with 18 different treatment regimens for advanced melanoma involving 10,090 patients were included. Overall, nivolumab 1 mg/kg plus ipilimumab 3 mg/kg treatment regimen were associated with the highest beneficial effect on OS, PFS, and DCR. Closely followed by nivolumab 3 mg/kg plus ipilimumab 1 mg/kg, and nivolumab plus relatlimab treatment regimens. However, three regimens had less favorable safety profiles. Although ipilimumab 0.3 mg/kg was ranked as the best options with the lowest risk of grade ≥ 3 treatment or immune-related adverse events, less therapeutic benefit was performed. The pembrolizumab 10 mg/kg regimen may be the preferred treatment with relative higher efficiency and safety among the ICIs regimens reported, as well as the nivolumab 3 mg/kg regimen. Head-to-head trials showed similar results.
This study shown the preferred treatment regimens with relatively higher efficiency and safety among the reported ICI regimens. Our results may complement the current standard of care, while its direct drug comparisons will aid future trials.
免疫检查点抑制剂（ICIs）已进入不可切除的晚期黑色素瘤的治疗模式，但缺乏关于其相对疗效和安全性的证据。本研究旨在比较ICIs在晚期不可切除黑色素瘤患者中的疗效和安全性。
纳入的研究包括比较ICIs、ICIs联合治疗、或与化疗药物、不同ICIs、或不同给药方案的一种ICIs的随机临床试验（RCTs）。遵循PRISMA报告指南进行贝叶斯网络荟萃分析的随机效应模型。主要结局为总生存期（OS）和无进展生存期（PFS）。次要结局包括客观缓解率（ORR）、疾病控制率（DCR）和不良事件。
国际前瞻性系统评价注册库（PROSPERO）：CRD42021229086。
纳入了24项RCTs，涉及10,090例患者，有18种不同的晚期黑色素瘤治疗方案。总体而言，纳武利尤单抗1mg/kg加伊匹木单抗3mg/kg治疗方案对OS、PFS和DCR的有益效果最高。紧随其后的是纳武利尤单抗3mg/kg加伊匹木单抗1mg/kg，以及纳武利尤单抗加瑞派利单抗治疗方案。然而，有三种方案的安全性较差。尽管伊匹木单抗0.3mg/kg被列为≥3级治疗或免疫相关不良事件风险最低的最佳选择，但治疗益处较小。帕博利珠单抗10mg/kg方案可能是所报告的ICIs方案中效率和安全性相对较高的首选治疗方案，纳武利尤单抗3mg/kg方案也是如此。头对头试验显示了类似的结果。
本研究显示了所报告的ICI方案中效率和安全性相对较高的首选治疗方案。我们的结果可能补充当前的治疗标准，而其直接的药物比较将有助于未来的试验。
