Stepping on the Gas or Hitting the Brakes: Response-Driven Therapy for Melanoma

Immunotherapy and BRAF-targeted therapy strategies reduce recurrence risk and improve survival in patients with high-risk resected and metastatic melanoma, respectively. Optimizing the use of these treatment options can maximize clinical benefit and reduce exposure to adverse events and cost and burden of care for patients. In high-risk resectable disease, neoadjuvant anti-PD-1 monotherapy and anti-PD-1/anti-CTLA-4 combination therapy demonstrate greater event-free survival compared with adjuvant therapy alone and can be used to guide de-escalation of treatment in patients with major pathologic responses or a change in therapy in patients with suboptimal responses. In patients with metastatic disease, selection of frontline anti-PD-1-based therapy can incorporate multiple factors when making decisions with patients including subtype of melanoma, extent of disease, risk of adverse events, and salvage options. While consideration of toxicity risk is important, more aggressive up-front strategies can lead to better off-treatment survival outcomes. Duration of therapy to achieve maximal benefit continues to be an area of investigation with the depth of response potentially being a key biomarker. Strategies such as post-treatment positron emission tomography/computed tomography scan for assessment of residual active disease may guide these decisions. In patients with no evidence of post-treatment active disease, shorter durations of therapy may be feasible without diminished efficacy. When active disease remains, risk for progression is heightened and continuation/escalation of treatment is warranted.