Neoadjuvant immunotherapy in melanoma: pathological response as a surrogate endpoint?

This review evaluates by analyzing recent studies whether pathological complete response (pCR) can be used as a reliable surrogate marker for overall survival (OS) in melanoma treated with neoadjuvant immunotherapy.

Trials like Neo-Combi, Neo-Trio and COMBI-Neo show that pCR is crucial for long-term success in targeted therapy for melanoma, while studies like OpACIN-neo and SWOG S1801 demonstrate that immunotherapy can provide durable benefits even with partial responses. Findings from NADINA and the INMC analysis highlight that immunotherapy achieves higher pathologic response rates and improved survival outcomes, offering broader benefits compared to the pCR-dependent outcomes of targeted therapy.

pCR serves as a critical prognostic biomarker across cancer types, with strong validation in breast cancer where it predicts long-term survival, particularly in aggressive subtypes like triple-negative and HER2-positive breast cancer. In melanoma, pCR is gaining prominence as a surrogate marker in neoadjuvant therapies, with its predictive value varying between targeted treatments - where achieving pCR is essential - and immunotherapies, which provide durable survival benefits even with partial responses. Despite its potential, the role of pCR as a universally reliable surrogate endpoint in melanoma requires further validation through cancer-specific studies to ensure accurate treatment guidance and personalized care.