AUTHOR=Sheng Feng , Yan Yulan , Zeng Baoqi 

TITLE=Efficacy and safety of immune checkpoint inhibitors and targeted therapies in resected melanoma: a systematic review and network meta-analysis

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1284240

DOI=10.3389/fphar.2023.1284240

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Multiple immune checkpoint inhibitors (ICIs) and targeted therapies have been widely used as adjuvant treatments for high-risk resected melanoma, with unclear comparative efficacy and safety.</p><p><bold>Methods:</bold> PubMed, Embase, the Cochrane Library, and <ext-link ext-link-type="uri" xlink:href="http://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link> were searched from database inception until 6 June 2023. We included RCTs that assess adjuvant ICIs or targeted therapies in high-risk resected melanoma. Frequentist random-effect network meta-analyses (NMA) were performed. The primary outcome was recurrence-free survival (RFS).</p><p><bold>Results:</bold> Eleven trials including 10,712 patients and comparing 10 treatments (nivolumab [Nivo], ipilimumab 3 mg/kg [Ipi3], Ipi10, pembrolizumab [Pemb], vemurafenib [Vemu], bevacizumab [Beva], Nivo + Ipi1, Nivo + Ipi3, dabrafenib plus trametinib [Dab + Tram], and placebo/observation [Pla/Obs]) were included. NMA showed that all treatments showed RFS benefit over placebo/observation except Ipi3 (hazard ratio [HR], 0.78; 95% CI, 0.58–1.05). Combination therapy of Nivo + Ipi3 was the most effective treatment, which significantly improved RFS compared with other treatments. NMA also showed that all treatments were associated with an increased risk of grade 3-5 adverse events over placebo/observation except Nivo (HR, 1.25; 95% CI, 0.87–1.80). NMA suggested that Nivo and Pemb were the two safest treatments except for placebo/observation. Although three combination therapies ranked as the top three in terms of RFS, they did not show significant overall survival benefits compared to monotherapies including Pemb, Nivo, Ipi3, and Ipi10.</p><p><bold>Conclusion:</bold> In this NMA, adjuvant Nivo and Pemb are the preferred options in patients with resected melanoma considering the benefits and harms. Combination therapy of Nivo + Ipi3 may be a promising strategy, but more evidence from phase 3 trials is needed.</p><p><bold>Systematic Review Registration:</bold><ext-link ext-link-type="uri" xlink:href="https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=438667" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=438667</ext-link>, PROSPERO (CRD42023438667).</p>