Eljilany Islam, Castellano Ella, Tarhini Ahmad A
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Emory College of Arts and Sciences, Emory University, Atlanta, GA 30322, USA.
Cancers (Basel). 2023 Aug 16;15(16):4125. doi: 10.3390/cancers15164125.
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.
对于因黑色素瘤复发风险和黑色素瘤死亡率增加而接受手术切除的IIB-IV期黑色素瘤患者，建议考虑全身辅助治疗。在过去三十年中测试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（达拉非尼-曲美替尼用于BRAF突变型黑色素瘤）、放疗和化疗。如随机试验所报道，这些疗法中的大多数已被证明可提高无复发生存期（RFS），但对总生存期（OS）的影响有限或没有影响。在当代临床实践中，由于观察到这些治疗可显著提高RFS，手术切除的III-IV期黑色素瘤的辅助治疗方法已明显转向使用纳武利尤单抗、帕博利珠单抗和BRAF-MEK抑制剂，如达拉非尼加曲美替尼（专门用于BRAF突变型黑色素瘤）。帕博利珠单抗已在美国获得监管批准，用于治疗切除的IIB-IIC期黑色素瘤，而纳武利尤单抗目前正在接受相同适应症的审查。本综述全面分析了辅助治疗中已完成的III期辅助治疗试验。此外，它还提供了正在进行的试验的总结以及辅助治疗的主要挑战和未来方向的概述。
