Neoadjuvant Therapy and the Evolving Management of Resectable Advanced Melanoma

Area of Science:

• Oncology
• Immunology
• Surgical Oncology

Background:

• Melanoma presents complex challenges, with early stages often curable by surgery but with a risk of relapse.
• Traditional treatment for resectable stage III melanoma involved surgery followed by adjuvant therapy.
• Recent advances include neoadjuvant immunotherapy, aiming to enhance the immune response against the intact tumor before surgery.

Purpose of the Study:

• To evaluate the efficacy of neoadjuvant immune checkpoint inhibitors in resectable stage III melanoma.
• To establish pathological response as an early indicator of long-term outcomes.
• To explore response-adapted treatment strategies and potential predictive biomarkers.

Main Methods:

• Review of prospective neoadjuvant studies (OpACIN, OpACIN-neo, PRADO, SWOG S1801, NADINA).
• Analysis of pathological response rates and event-free survival.
• Investigation of biomarkers (PD-L1, IFN-γ signature, tumor mutational burden, PET scans) for response prediction.

Main Results:

• Neoadjuvant ipilimumab plus nivolumab demonstrated high pathological response rates.
• Perioperative pembrolizumab showed improved event-free survival compared to adjuvant therapy alone.
• The NADINA trial confirmed improved outcomes with neoadjuvant ipilimumab plus nivolumab and response-adapted adjuvant therapy.

Conclusions:

• Neoadjuvant immunotherapy is a viable and effective strategy for resectable stage III melanoma.
• Pathological response serves as a crucial early marker for treatment benefit.
• Further validation of biomarkers is needed for routine clinical application in guiding treatment decisions.