Survival benefits and toxicity effects of radiotherapy and immunotherapy treatments in melanoma patients with brain metastases: A meta-analysis

Objective

To compare the efficacy and toxicity of four treatment strategies in patients with MBMs.

Methods

A systematic literature search of the Cochrane, PubMed, Embase, Web of Science, and OVID Medline databases was performed until July 24, 2024. A total of four therapeutic modalities for MBMs, including immune checkpoint inhibitor (ICI) monotherapy, radiotherapy (RT) alone, ICI combined with RT (ICI ​+ ​RT), and dual ICI therapy (ICI ​+ ​ICI), were evaluated by the overall survival (OS), intracranial progression-free survival (iPFS), and adverse effect (AE). The meta-analysis was performed using R language and registered in PROSPERO (registration no. CRD42023480912).

Results

This study included 33 studies comprising 2,496 patients with MBMs. ICI combined with RT and dual ICI therapy improved the 6 and 12-month OS rates compared with ICI monotherapy and RT alone. There was no significant difference in OS between the ICI + RT group and the ICI + ICI group. Similar results were observed for iPFS, with the combination treatment groups showing a significant difference compared with the treatment groups alone. However, no significant difference was observed in 1-year iPFS between the ICI + RT group and the ICI + ICI group (P ​= ​0.07), whereas the ICI + ICI group demonstrated superior 2-year iPFS compared with the ICI + RT group (P ​< 0.05). Furthermore, the survival advantages of combination therapy gradually decreased with increasing duration of treatment. Additionally, compared with ICI monotherapy, dual ICI therapy significantly increased the incidence of AEs over grade 3 (ICI ​+ ​ICI: 57% vs. ICI: 11%, P ​< ​0.0001), whereas ICI combined with RT did not significantly differ (ICI ​+ ​RT: 19% vs. ICI: 11%, P ​= ​0.14).

Conclusion

The combination of ICI with RT offers superior survival benefits without increasing toxicity in patients with MBMs. However, this survival benefit decreases over time, and further optimizing the treatment strategy is essential for improving the outcomes of patients with MBMs.