Department of Surgery, Duke University Medical Center, Durham, NC, USA.
Department of Surgery, Cedars-Sinai Health System, Los Angeles, CA, USA.
Ann Surg Oncol. 2024 Mar;31(3):1851-1856. doi: 10.1245/s10434-023-14702-x. Epub 2023 Dec 10.
Modern effective systemic therapy for melanoma includes two important classes of treatment: immune checkpoint inhibitors (ICIs), comprising inhibitors of cytotoxic T-lymphocyte antigen 4, programmed cell death receptor 1, and lymphocyte-activation gene 3; and small molecule BRAF/MEK inhibitor therapy. These treatments have revolutionized the management of patients with advanced melanoma and have dramatically improved clinical outcomes. The melanoma treatment landscape continues to evolve as outcome data from completed trials continue to mature and as newer studies begin to report data. In 2022 and 2023, longer-term follow-up data for established single-agent ICI therapy has been published improving our understanding of both efficacy and durability of treatment responses. A trial of a novel combination ICI therapy has demonstrated enhanced efficacy, and a study examining the order/sequence of ICI therapy versus BRAF/MEK inhibitor therapy for first-line treatment of metastatic melanoma showed that survival is improved when patients start with ICI therapy. As the indications for these therapies have expanded to the adjuvant and neoadjuvant space, we also saw the publication of 5-year results of adjuvant therapy in resected stage III patients, new data on the role of adjuvant therapy in resected stage IIB and IIC patients, and, finally, a practice-changing trial demonstrating improved outcomes using a neoadjuvant approach for patients with macroscopic disease amenable to surgical resection. In this article, we review these articles and highlight key elements for surgical oncologists.
免疫检查点抑制剂(ICIs),包括细胞毒性 T 淋巴细胞抗原 4、程序性细胞死亡受体 1 和淋巴细胞激活基因 3 的抑制剂;以及小分子 BRAF/MEK 抑制剂治疗。这些治疗方法彻底改变了晚期黑色素瘤患者的治疗管理方式,并显著改善了临床结果。随着完成的试验的结果数据继续成熟,以及新的研究开始报告数据,黑色素瘤治疗领域仍在不断发展。在 2022 年和 2023 年,发表了关于已确立的单一 ICI 治疗的更长随访数据,这提高了我们对治疗反应的疗效和持久性的理解。一项新型联合 ICI 治疗的试验显示出增强的疗效,一项研究检查了 ICI 治疗与 BRAF/MEK 抑制剂治疗用于转移性黑色素瘤一线治疗的顺序/序列,结果表明,当患者开始 ICI 治疗时,生存得到改善。随着这些疗法的适应症扩展到辅助和新辅助治疗领域,我们还看到了辅助治疗在 III 期可切除患者中的 5 年结果、辅助治疗在 IIB 和 IIC 期可切除患者中的作用的新数据,以及最后,一项改变实践的试验表明,对于可手术切除的宏观疾病患者,采用新辅助方法可改善预后。在本文中,我们回顾了这些文章,并强调了外科肿瘤学家的关键要素。