P14.25 Melanoma brain metastases in the era of novel therapies: a single-center, Dutch cohort study

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Abstract BACKGROUND Until recently, patients with melanoma brain metastases (MBMs) had limited therapeutic options. With the arrival of immune checkpoint inhibitors (ICIs), targeted therapy (TT) and advances in stereotactic radiotherapy (SRT), treatment has improved. We evaluated treatments and patient outcome before and after the introduction of these novel therapies. MATERIAL AND METHODS In this retrospective, single-center study, patients presenting with MBMs at the Erasmus MC between November 2005 and January 2021 with sufficient follow-up were included. Overall survival (OS), measured from date of MBM diagnosis, was calculated using the Kaplan-Meier method. Patients were stratified according to MBM diagnosis before and after January 1, 2016, since novel therapies were mostly prescribed in our clinic after this date. Results were significant (p<0.05), unless otherwise stated. RESULTS Overall, 413 patients were included. Median [IQR] age was 56.6 years [52–71] with a 60% male predominance. A BRAF mutation was present in 46.7% of patients. A single MBM was found in 29.3% and ≥4 MBMs were found in 49.0% of patients. Before January 1, 2016, 191 patients were treated, and 222 patients after that date. Chemotherapy was more frequently used before 2016, both prior to (3.9% pre-2016 vs. 0.9% post-2016) and after (7.0% vs. 0.0%) the diagnosis of MBMs. In contrast, treatment with TT was more frequent after 2016, both prior to (3.7% vs. 16.2%) and after (7.9% vs. 41.4%) the diagnosis of MBMs. Comparable changes were observed for treatment with ICIs (prior to MBM diagnosis: 0.5% vs. 25.2%; after MBM diagnosis: 18.3% vs 39.2%). The application of SRT did not differ significantly before and after 2016 (12.0% vs. 19.4%, p=0.89), while the application of whole brain radiotherapy (WBRT) decreased (52.4% vs. 13.5%). Surgical resection was not significantly different between those periods (15.7% vs. 16.7%, p=0.90). Before 2016, median OS [IQR] was shorter than after 2016 (4.6 [1.9–10.9] vs. 6.6 [1.8–24.5] months). The effect of novel therapies on OS was further analysed in patients diagnosed after 2016; treatment vs. no treatment was compared. ICI treatment prior to MBM diagnosis was associated with worse OS (median OS 4.0 vs. 7.5 months). ICI treatment after MBM diagnosis was associated with better OS (median OS 24.5 vs. 3.0 months). In patients with a BRAF mutation, TT before MBM diagnosis was associated with worse OS (median OS 1.8 vs. 9.4 months). TT after MBM diagnosis in those patients was not significantly associated with improved OS (median OS 7.6 vs. 5.2 months, p=0.96). CONCLUSION Recent therapeutic advances for MBM replaced WBRT and chemotherapy with SRT, TT and ICIs. In that period, prognosis of MBM patients increased significantly. OS in patients treated with ICIs or TT prior to MBM diagnosis is still poor, but OS is improved in patients treated with ICIs after the diagnosis of MBM.