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Personalized Neoadjuvant Immunotherapy for Stage III Melanoma: Survival Insights

By: Amanda E. Ruffino, MD
Posted: Friday, January 31, 2025

Pathologic response to neoadjuvant immune checkpoint blockade in stage III melanoma is associated with survival outcomes, enabling the development of personalized, response-directed treatment strategies, according to a comparison of data from two clinical trials. Christian U. Blank, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, and colleagues revealed that for patients achieving a major pathologic response, therapeutic lymph node dissection and adjuvant systemic therapy can potentially be omitted without adversely affecting recurrence-free or distant metastasis–free survival. However, for patients without a pathologic response, adjuvant systemic therapy appears to significantly improve survival metrics.

“Although these results are hypothesis-generating and require further validation, they offer a potential foundation for developing personalized neoadjuvant immunotherapy approaches,” the study authors noted.

This analysis compared survival outcomes from the phase II OpACIN-neo and PRADO trials, which evaluated the effects of neoadjuvant treatment with the CTLA-4 inhibitor ipilimumab and the PD-1 inhibitor nivolumab in stage III melanoma. OpACIN-neo employed a nonpersonalized approach, in which all patients underwent therapeutic lymph node dissection and received no adjuvant therapy. In contrast, PRADO employed a response-directed approach, omitting therapeutic lymph node dissection and adjuvant therapy for patients achieving a major pathologic response, while administering both to patients without a pathologic response.

Among patients achieving a major pathologic response, the 3-year recurrence-free survival was 93% for those without therapeutic lymph node dissection and 96% for those with it (P = .47). Distant metastasis–free survival was 98% and 96%, respectively (P = .49). This indicates no significant survival benefit from therapeutic lymph node dissection in this subgroup, according to the investigators. Conversely, patients without a pathologic response who received adjuvant systemic therapy demonstrated improved 3-year recurrence-free survival (64% vs 35%, P = .10) and distant metastasis–free survival (70% vs 52%, P = .24) compared with those who did not receive it.

Disclosure: For full disclosures of the study authors, visit www.ejcancer.com


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