Department of Oncology, The University of Oxford, Oxford, OX 37LE, UK.
Am J Clin Dermatol. 2022 May;23(3):331-338. doi: 10.1007/s40257-022-00681-4. Epub 2022 Mar 31.
Increasing knowledge about the biology of melanoma and of immunology has led to the development and regulatory approval of the immune checkpoint inhibitors ipilimumab, nivolumab, and pembrolizumab, which are indicated for the treatment of melanoma irrespective of the B-Raf proto-oncogene mutation status of the tumour. Only a subset of patients will respond, but those who do can expect long-lasting, previously unheard-of responses. Long-term survival results for the registration trials, including CheckMate 067, Keynote-006, and Keynote-001, have recently been published. In particular, the combination of ipilimumab and nivolumab showed an impressive 5-year overall survival of just over 50%. However, toxicity remains a significant concern, with some of the side effects being life threatening and/or life changing. In this review, we discuss the safety and efficacy data of all the agents currently approved for the first-line treatment of advanced melanoma, identifying factors that influence the choice of a single agent rather than combination therapy. We highlight the potential biomarkers of response, effects of long-term toxicity, and options after progression.
对黑色素瘤生物学和免疫学的认识不断提高，促使免疫检查点抑制剂伊匹单抗、纳武单抗和派姆单抗的开发和监管批准，这些药物被批准用于治疗黑色素瘤，无论肿瘤的 B-Raf 原癌基因突变状态如何。只有一部分患者会有反应，但那些有反应的患者可以期待长期的、以前闻所未闻的反应。最近公布了注册试验的长期生存结果，包括 CheckMate 067、Keynote-006 和 Keynote-001。特别是，伊匹单抗和纳武单抗联合治疗显示出令人印象深刻的 5 年总生存率略高于 50%。然而，毒性仍然是一个严重的问题，一些副作用是危及生命的，和/或改变生活。在这篇综述中，我们讨论了目前批准用于晚期黑色素瘤一线治疗的所有药物的安全性和疗效数据，确定了影响选择单一药物而非联合治疗的因素。我们强调了反应的潜在生物标志物、长期毒性的影响以及进展后的选择。
