Kakish Hanna H, Ahmed Fasih Ali, Elshami Mohamedraed, Loftus Alexander W, Hoehn Richard S, Ammori John B, Ocuin Lee M, Winter Jordan M, Bordeaux Jeremy S, Mangla Ankit, Rothermel Luke D
Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.
Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.
Cancers (Basel). 2022 Oct 22;14(21):5184. doi: 10.3390/cancers14215184.
Several drugs and treatment modalities are under investigation to improve current melanoma therapy options. This review profiles the trends in clinical trial investment in late-stage melanoma, and anticipates what changes are expected in melanoma treatment, with a focus on exploratory drug mechanisms.
We reviewed nine international clinical trial databases for registered, interventional, and phase 3 cutaneous melanoma clinical trials since 2010.
73 trials studied drug therapies in late-stage (stage III and IV) melanoma. Exploratory mechanisms were investigated in 32% (23/73) of the late-stage melanoma drug therapy trials. Most exploratory drug trials include immunotherapy drug mechanisms (15/23 trials). Two exploratory mechanisms showed promise: the anti-LAG3 antibody, relatlimab, and the hapten modified vaccine, MVax. Many (52%) trials of exploratory mechanisms are ongoing including the use of adoptive cell transfer immunotherapies, dendritic cell vaccine therapy, and histone deacetylase (HDAC) inhibitors, among others.
Since most clinical trials focus on previously approved drug mechanisms, it is likely that paradigm-changing treatments will involve these therapies being used in new treatment contexts or combinations. Only 2 exploratory drug mechanisms studied since 2010 have achieved promising results in the phase 3 setting, though many other trials are ongoing at this time.
目前正在研究多种药物和治疗方式，以改善现有的黑色素瘤治疗方案。本综述概述了晚期黑色素瘤临床试验投资的趋势，并预测黑色素瘤治疗可能出现的变化，重点关注探索性药物机制。
我们检索了9个国际临床试验数据库，以获取自2010年以来注册的、介入性的3期皮肤黑色素瘤临床试验。
73项试验研究了晚期（III期和IV期）黑色素瘤的药物治疗。在32%（23/73）的晚期黑色素瘤药物治疗试验中研究了探索性机制。大多数探索性药物试验包括免疫治疗药物机制（15/23项试验）。两种探索性机制显示出前景：抗LAG3抗体relatlimab和半抗原修饰疫苗MVax。许多（52%）探索性机制试验正在进行，包括过继性细胞转移免疫疗法、树突状细胞疫苗疗法和组蛋白脱乙酰酶（HDAC）抑制剂等的应用。
由于大多数临床试验关注的是先前已批准的药物机制，改变范式的治疗可能涉及在新的治疗背景下或联合使用这些疗法。自2010年以来研究的探索性药物机制中，只有2种在3期试验中取得了有前景的结果，不过目前还有许多其他试验正在进行。
