ASO Author Reflections: Adjuvant Treatment of Melanoma in the Modern Era

Excerpt

In 2015, systemic ipilimumab was approved by the Food and Drug Administration (FDA) for patients with metastatic melanoma, but the severe toxicities limited its widespread adoption in the adjuvant setting.1 In 2017 the FDA approved adjuvant human IgG4 monoclonal antibody against programmed death 1 (anti-PD-1), which was associated with an improved recurrence-free survival (RFS) and fewer treatment-related adverse events in patients with resected stage III melanoma compared with ipilimumab.2 Also in 2017, trials investigating the efficacy of BRAF plus MEK inhibitors (BRAF/MEKi) in the adjuvant setting showed an improved RFS and overall survival (OS) in resected stage III melanoma patients with a BRAF V600 mutation.3 These studies have transformed the adjuvant management of patients with resected stage III and IV melanoma. However, the majority of these trials were completed in patients who underwent completion lymphadenectomy as standard of care for sentinel lymph node biopsy (SLNB) positive disease. Concurrent with the FDA approval of anti-PD1 and BRAF/MEKi in the adjuvant setting, the Multicenter Selective Lymphadenectomy Trial 2 (MSLT-2) was published, which demonstrated that close nodal observation of patients with resected melanoma who had low-burden stage III disease had similar melanoma-specific survival as patients who underwent immediate CLND.4 This management strategy has been widely adopted and is the preferred pathway in the National Comprehensive Cancer Network (NCCN) guidelines. Due to the rapid and concurrent changes in both surgical practice and adjuvant medical therapies, the adjuvant outcomes of patients treated according to the current MSLT-2 guidelines has not been previously assessed. …