Neoadjuvant therapy for melanoma: rationale for neoadjuvant therapy and pivotal clinical trials

The treatment of malignant melanoma has drastically changed over the past decade with the advent of immune checkpoint blockade, targeted therapy with BRAF/MEK inhibition, and other novel therapies such as oncolytic virus intralesional therapy. Despite improvements in patient response rates and survival with these new treatments, there exists a large portion of patients with surgically resectable disease that are high risk for relapse. Patients with high-risk resectable melanoma account for up to 20% of newly diagnosed cases. For this high-risk group of patients, neoadjuvant therapy has many purposed advantages over adjuvant therapy, including a more robust immune response due to abundant tumor antigens at treatment initiation, the ability to assess pathologic response to therapy, tumor downstaging leading to increased disease resectability, and a potential decreased need for extensive lymphadenectomies. These findings have been backed by preclinical models and multiple neoadjuvant trials are underway. In this review, we will discuss the trials that have set the foundation for the current treatment standards and discuss the role and rationale for neoadjuvant therapy for high-risk malignant melanomas.