Dimitriou F, Long G V, Menzies A M
Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Royal North Shore Hospital, Sydney, Australia; Mater Hospital, Sydney, Australia.
Ann Oncol. 2021 Jul;32(7):854-865. doi: 10.1016/j.annonc.2021.03.198. Epub 2021 Mar 24.
Patients with resected stage III and IV melanoma have a high risk of recurrence. As the outcomes for patients with metastatic disease have improved dramatically over the past decade due to systemic therapy, more recently so too have the outcomes of patients with resected stage III and IV melanoma with the introduction of checkpoint inhibitor immunotherapy and targeted therapy in the adjuvant setting.
This review outlines the latest clinical trial data, the current adjuvant treatment landscape and its application to clinical practice and expected future progress for the management of early-stage melanoma.
Anti-programmed cell death protein 1 monotherapy and BRAF/MEK inhibitors are currently deemed standard of care for resected stage III melanoma. For patients with stage IIIB [American Joint Committee on Cancer staging system version 7 (AJCCv7)] melanoma, 2-year and 3-year recurrence-free survival is approximately 72% and 65% for nivolumab, 70% and 65.7% for pembrolizumab and 68% and 60% for dabrafenib/trametinib, respectively. For stage IIIC (AJCCv7) melanoma, 2-year and 3-year recurrence-free survival is 60% and 53.5% for nivolumab, 60% and 54.3% for pembrolizumab and 59% and 47% for dabrafenib/trametinib, respectively. Adjuvant treatment is recommended for patients with stage IIIB-IIID [AJCC staging system version 8 (AJCCv8)] melanoma, and may be considered for patients with stage IIIA melanoma. For resected stage IV, nivolumab is the only approved agent; however, recent results from a phase II clinical trial show promising efficacy for combined ipilimumab and nivolumab as well. Long-term data are required to determine which therapy has the greatest impact on overall survival. Schedules, delivery and toxicity are also important factors to consider when selecting adjuvant treatment.
Randomized studies of patients with resected high-risk melanoma have shown that immunotherapy or targeted therapy improve recurrence-free survival compared with placebo/ipilimumab. In order to optimize these treatments, prognostic and predictive biomarkers, as well as strategies to reduce treatment-related toxicities and overcome resistance, are required.
接受切除的III期和IV期黑色素瘤患者复发风险高。在过去十年中，由于全身治疗，转移性疾病患者的预后有了显著改善，最近，随着辅助治疗中引入检查点抑制剂免疫疗法和靶向疗法，接受切除的III期和IV期黑色素瘤患者的预后也有所改善。
本综述概述了最新的临床试验数据、当前的辅助治疗情况及其在临床实践中的应用，以及早期黑色素瘤管理的预期未来进展。
抗程序性细胞死亡蛋白1单药疗法和BRAF/MEK抑制剂目前被视为切除的III期黑色素瘤的标准治疗方案。对于IIIB期[美国癌症联合委员会分期系统第7版（AJCCv7）]黑色素瘤患者，纳武单抗的2年和3年无复发生存率分别约为72%和65%，帕博利珠单抗分别为70%和65.7%，达拉非尼/曲美替尼分别为68%和60%。对于IIIC期（AJCCv7）黑色素瘤，纳武单抗的2年和3年无复发生存率分别为60%和53.5%，帕博利珠单抗分别为60%和54.3%，达拉非尼/曲美替尼分别为59%和47%。对于IIIB-IIID期[美国癌症联合委员会分期系统第8版（AJCCv8）]黑色素瘤患者，推荐进行辅助治疗，对于IIIA期黑色素瘤患者可考虑进行辅助治疗。对于切除的IV期患者，纳武单抗是唯一获批的药物；然而，一项II期临床试验的最新结果显示，伊匹木单抗和纳武单抗联合使用也具有良好的疗效。需要长期数据来确定哪种疗法对总生存期影响最大。在选择辅助治疗时，治疗方案、给药方式和毒性也是需要考虑的重要因素。
对接受切除的高危黑色素瘤患者进行的随机研究表明，与安慰剂/伊匹木单抗相比，免疫疗法或靶向疗法可提高无复发生存率。为了优化这些治疗，需要预后和预测生物标志物，以及降低治疗相关毒性和克服耐药性的策略。
