Systemic treatment strategies for BRAF wild-type metastatic unresectable melanoma: a network meta-analysis

This study aimed to provide new insights into systemic treatment for BRAF wild-type metastatic unresectable melanoma, thereby offering a basis for personalized clinical decision-making.

PubMed, Embase, Cochrane Library, and Web of Science were searched. Eligible participants were adults with pathologically confirmed BRAF V600 wild-type metastatic unresectable melanoma. Outcomes included progression-free survival (PFS) and overall survival (OS). Network meta-analysis (NMA) results were presented as league tables and the surface under the cumulative ranking curve (SUCRA) values.

In total, 8 randomized controlled trials (RCTs) involving 3,418 patients and 9 systemic treatment strategies were included. One open-label study was rated as having some concerns, while the remaining seven were rated as low risk of bias across all domains and overall. The NMA results showed that, compared to ipilimumab, pembrolizumab, nivolumab, nivolumab + relatlimab, and nivolumab + ipilimumab demonstrated significant advantages in improving OS. Notably, nivolumab + relatlimab ranked first in prolonging OS (SUCRA = 93.94%). In the PFS analysis, this regimen had the highest SUCRA value only within the connected network consisting of dacarbazine, nivolumab, and the combination of nivolumab and relatlimab (SUCRA = 98.86%), although no comparisons or standardized rankings were performed between different PFS networks.

The results of OS primary analysis for nivolumab plus relatlimab, as well as its ranking within the corresponding PFS network, are exploratory in nature. They are intended solely to generate research hypotheses and should not be interpreted as evidence of superiority over other treatments or as a basis for changing the current standard of care. Direct head-to-head RCTs are still needed to further clarify the comparative efficacy of the relevant regimens.