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 last decade due to systemic therapy, more recently have the outcomes of patients improved 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-PD1 monotherapy and BRAF/MEK inhibitors are currently deemed standard-of-care for resected stage III melanoma. For patients with stage IIIB (AJCCv7) melanoma, 2-year and 3-year recurrence-free survival (RFS) 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 RFS 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 (AJCCv8), and may be considered for patients with 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 is 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.
Florentia Dimitriou, Georgina V Long, Alexander M Menzies