Preoperative therapy in melanoma: Evolving perspectives in clinical trials

We reviewed phase II and III trials beginning after 2010 studying preoperative therapy in melanoma (61 trials). Compared to standard adjuvant treatment, neoadjuvant immune checkpoint inhibitors (ICIs) show improved outcomes with approximately 70–80% recurrence free survival at 2 years. Several biomarkers demonstrate predictive value for pathological response (higher PD-L1 expression) and survival (IFN-γ signatures, CD8 + cell density). A number of ‘non-standard’ treatment mechanisms are being studied in combination with ICI therapies such as TLR-9 agonists, and anti-LAG3 checkpoint inhibitors, which show promise for alternative therapy options in the neoadjuvant setting. Finally, trials for advanced unresectable melanomas show improved survival compared to definitive systemic treatment when upfront systemic therapies lead to resectability. To conclude, in the preoperative setting for melanoma, ICIs have potential to improve outcomes for patients, and will likely change the standard treatment approach for advanced resectable disease. [Display omitted] •There are currently no approved FDA neoadjuvant treatments for melanoma.•We identified 61 clinical trials in neoadjuvant melanoma across nine databases.•ICIs have potential to improve outcomes for patients in the neoadjuvant setting.•BRAF/MEK inhibitors and ICI led to resectability of previously unresectable melanomas.•Alternative therapy mechanisms are being studied in combination with ICIs in the neoadjuvant setting.