LAUSR

Simple Summary Cutaneous melanoma is highly prone to metastasize to the brain, with a historically poor overall survival of only 4–5 months. Over the past decade, novel drugs such as targeted therapies and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma. However, most prospective studies have excluded patients with melanoma brain metastasis (MBM) or included only patients with stable (steroid-free) or asymptomatic MBM. To assess the impact of novel treatments in patients with MBM in a real-world setting, we studied a cohort of consecutive patients over a period of sixteen years (2005 to 2021) in a large, tertiary referral center for melanoma (Erasmus MC, Rotterdam, the Netherlands). We found a significant improvement in overall survival in the modern (post-2015) era, associated with stereotactic radiotherapy and especially ICIs. These findings support that ICIs, if clinically feasible, should be considered first in clinical practice after a diagnosis of MBM. Abstract Background: Melanoma brain metastasis (MBM) is associated with poor outcome, but targeted therapies (TTs) and immune checkpoint inhibitors (ICIs) have revolutionized treatment over the past decade. We assessed the impact of these treatments in a real-world setting. Methods: A single-center cohort study was performed at a large, tertiary referral center for melanoma (Erasmus MC, Rotterdam, the Netherlands). Overall survival (OS) was assessed before and after 2015, after which TTs and ICIs were increasingly prescribed. Results: There were 430 patients with MBM included; 152 pre-2015 and 278 post-2015. Median OS improved from 4.4 to 6.9 months (HR 0.67, p < 0.001) after 2015. TTs and ICIs prior to MBM diagnosis were associated with poorer median OS as compared to no prior systemic treatment (TTs: 2.0 vs. 10.9 and ICIs: 4.2 vs. 7.9 months, p < 0.001). ICIs directly after MBM diagnosis were associated with improved median OS as compared to no direct ICIs (21.5 vs. 4.2 months, p < 0.001). Stereotactic radiotherapy (SRT; HR 0.49, p = 0.013) and ICIs (HR 0.32, p < 0.001) were independently associated with improved OS. Conclusion: After 2015, OS significantly improved for patients with MBM, especially with SRT and ICIs. Demonstrating a large survival benefit, ICIs should be considered first after MBM diagnosis, if clinically feasible.