Neoadjuvant Therapy in Melanoma: Where Are We Now?

Melanoma systemic therapy has witnessed major advances with the development of immune checkpoint inhibitors and molecularly targeted therapy that have been translated into the neoadjuvant setting in managing locoregionally advanced disease. PD1 blockade as monotherapy and combined with CTLA4 blockade or LAG3 inhibition has demonstrated major improvements in reducing the risk of relapse and death that were associated with high pathologic response rates. Similar results were reported with BRAF-MEK inhibition for BRAF mutant melanoma with high pathologic response rates that appear to be less durable compared to immunotherapy. More importantly, in a recent randomized trial, event-free survival was significantly improved with neoadjuvant pembrolizumab compared to standard surgery and adjuvant therapy. Neoadjuvant therapy has become the standard of care for locoregionally advanced melanoma. Ongoing studies will define the most optimal combination regimens.