Department of Dermatology, Allergology and Venerology, University Medical Center Schleswig-Holstein, Campus Lübeck; Department of Internal Medicine III, Hematology and Oncology, University Hospital rechts der Isar, TU München; Department of Dermatology University of Tübingen.
Dtsch Arztebl Int. 2019 Jul 22;116(29-30):497-504. doi: 10.3238/arztebl.2019.0497.
The systemic treatment of metastatic melanoma has improved considerably with the introduction of new, targeted substances and immune checkpoint inhibitors. This article presents treatment options for advanced inoperable melanoma and in the setting of adjuvant treatment after complete metastasectomy.
The data for analysis were derived from a selective literature search in PubMed and a search for systematic reviews in the Cochrane Library.
Immune checkpoint inhibitors, which target the cytotoxic T-lymphocyte antigen or the "programmed death" (PD) receptor, activate T-cells and other immune cells, so that the body's own immune system attacks the melanoma. In unselected patients, immune checkpoint inhibition using nivolumab improved overall survival compared with dacarbazine (hazard ratio [HR]: 0.42; P<0.001). The antibody pem- brolizumab also led to better overall survival than ipilimumab (HR 0.68; P<0.001). Combination treatment with anti-CTLA-4 and anti-PD-1 antibodies improved overall survival even more than ipilimumab monotherapy, albeit at the cost of greater toxic- ity (HR 0.55; P<0.001). Another treatment approach aims to inhibit intracellular signal transduction in the melanoma cells. For patients with a BRAF-V66 mutation, combination treatments with BRAF/MEK inhibitors led to a rapid response in most cases (64-75%). In principle, the novel treatments are also effective in patients with cerebral metastases. In the adjuvant setting, both immune checkpoint inhibitors and BRAF/MEK inhibitors reduced the risk of recurrence by about 50%.
High-quality studies show that the new substances are clinically effective in the palliative and adjuvant treatment of melanoma.
随着新型靶向药物和免疫检查点抑制剂的出现，转移性黑色素瘤的全身治疗已显著改善。本文介绍了晚期不可切除黑色素瘤的治疗选择，以及完全转移切除术后辅助治疗的选择。
分析数据来源于在 PubMed 中进行的选择性文献检索和在 Cochrane 图书馆中进行的系统评价检索。
免疫检查点抑制剂靶向细胞毒性 T 淋巴细胞抗原或“程序性死亡”（PD）受体，激活 T 细胞和其他免疫细胞，使机体自身免疫系统攻击黑色素瘤。在未经选择的患者中，与达卡巴嗪相比，使用 nivolumab 的免疫检查点抑制改善了总生存期（风险比 [HR]：0.42；P<0.001）。抗体 pem- brolizumab 也导致总生存期优于 ipilimumab（HR 0.68；P<0.001）。抗 CTLA-4 和抗 PD-1 抗体的联合治疗甚至比 ipilimumab 单药治疗更能改善总生存期，但代价是更大的毒性（HR 0.55；P<0.001）。另一种治疗方法旨在抑制黑色素瘤细胞内的信号转导。对于存在 BRAF-V66 突变的患者，BRAF/MEK 抑制剂联合治疗在大多数情况下迅速产生反应（64-75%）。原则上，这些新的治疗方法在脑转移患者中也有效。在辅助治疗中，免疫检查点抑制剂和 BRAF/MEK 抑制剂都使复发风险降低了约 50%。
高质量的研究表明，新型药物在黑色素瘤的姑息和辅助治疗中具有临床疗效。
