The consideration of systemic adjuvant therapy is recommended for patients with stage IIB-IV melanoma who have undergone surgical resection due to a heightened risk of experiencing melanoma relapse and mortality from melanoma. Adjuvant therapy options tested over the past three decades include high-dose interferon-α, immune checkpoint inhibitors (pembrolizumab, nivolumab), targeted therapy (dabrafenib-trametinib for BRAF mutant melanoma), radiotherapy and chemotherapy. Most of these therapies have been demonstrated to enhance relapse-free survival (RFS) but with limited to no impact on overall survival (OS), as reported in randomized trials. In contemporary clinical practice, the adjuvant treatment approach for surgically resected stage III-IV melanoma has undergone a notable shift towards the utilization of nivolumab, pembrolizumab, and BRAF-MEK inhibitors, such as dabrafenib plus trametinib (specifically for BRAF mutant melanoma) due to the significant enhancements in RFS observed with these treatments. Pembrolizumab has obtained regulatory approval in the United States to treat resected stage IIB-IIC melanoma, while nivolumab is currently under review for the same indication. This review comprehensively analyzes completed phase III adjuvant therapy trials in adjuvant therapy. Additionally, it provides a summary of ongoing trials and an overview of the main challenges and future directions with adjuvant therapy.
对于已完成手术切除的IIB-IV期黑色素瘤患者，鉴于其存在较高的复发及死亡风险，建议考虑系统性辅助治疗。过去三十年间，经临床试验验证的辅助治疗方案包括高剂量干扰素-α、免疫检查点抑制剂（帕博利珠单抗、纳武利尤单抗）、靶向治疗（针对BRAF突变型黑色素瘤的达拉非尼-曲美替尼联合疗法）、放疗及化疗。随机试验数据显示，多数疗法虽能显著改善无复发生存期，但对总生存期的提升作用有限甚至无显著影响。当前临床实践中，针对手术切除后的III-IV期黑色素瘤，辅助治疗策略已显著转向使用纳武利尤单抗、帕博利珠单抗以及BRAF-MEK抑制剂（如达拉非尼联合曲美替尼，专用于BRAF突变型黑色素瘤），主要基于这些疗法在无复发生存期方面展现的显著改善。目前帕博利珠单抗已在美国获批用于治疗已切除的IIB-IIC期黑色素瘤，而纳武利尤单抗针对相同适应症的审批仍在进行中。本综述系统分析了已完成的III期辅助治疗临床试验，同时总结了当前进行中的试验，并对辅助治疗面临的主要挑战及未来发展方向进行了概述。
Adjuvant Therapy for High-Risk Melanoma: An In-Depth Examination of the State of the Field
肿瘤(癌症)患者之家