Real-world clinical outcomes of patients with BRAF-mutated melanoma with or without brain metastases receiving frontline immune-checkpoint inhibitors in the US community oncology setting.

Abstract

9542 Background: Patients with BRAF-mutated melanoma are at increased risk of melanoma brain metastasis (MBM) which has historically led to worse outcomes. The prognosis of patients with MBM has improved with approval of immune checkpoint inhibitors (ICI) and targeted therapy. However, there is limited information on the impact of the MBM on outcomes in patients with BRAF mutations treated with frontline (1L) ICI. This study aims to describe clinical outcomes of patients with BRAF-mutated metastatic melanoma treated with 1L ICI in the community oncology setting, with a focus on patients with MBM. Methods: This was a retrospective observational cohort study of patients with BRAF-mutated metastatic melanoma who initiated 1L ICI (index) between 1/1/16-6/30/22 in The US Oncology Network and non-Network practices and were followed through 6/30/24. Patient characteristics and genomic alterations were sourced from structured electronic health records data and genomic testing results. Patients with mucosal or uveal melanoma, clinical trial participation, treatment for other primary cancers or evidence of co-mutations were excluded. Kaplan-Meier analyses of overall survival (OS), real-world time to treatment discontinuation (rwTTD) and time to next treatment (rwTTNT) were assessed from index, overall and in patients with MBM. Results: Of 798 metastatic melanoma patients with a BRAF mutation, 41 (5%) had documentation of a co-mutation and were excluded, resulting in 757 patients in the final analysis set. Median follow-up was 14.6 months, and median age at index was 64 years. Among patients with available data, most were male (63%), White (97%) and had an ECOG of 0-1 (87% among reported) within 60 days prior to index. Among patients with mutation-specific data (n=704), the most common mutation types were V600E (83%) and other V600 (13%) point mutations. The most common 1L ICI regimens were nivolumab+ipilimumab (45%), pembrolizumab (30%), and nivolumab (22%). MBM was documented in 46 (6%) patients at 1L ICI treatment initiation, and an additional 28 (4%) patients developed MBM during the follow-up period, resulting in a total of 74 (10%) patients with MBM. Conclusions: Although lower-than-expected rates of MBM were observed, in this large real-world dataset from the community setting, patients with a BRAF mutation had similar rwTTD, rwTTNT, and OS following ICI therapy, irrespective of the presence of MBM. It is reasonable to consider combination ICI therapy in BRAF mutant melanoma patients diagnosed with MBM who lack known contraindications. Further research on the impact of the somatic mutational background on MBM outcomes is ongoing. Outcome, median (95% CI) Overall (N=757) MBM, any time (N=74) OS, months 20.3 (16.6, 25.8) 20.3 (10.4, 33.8) rwTTD, months 3.5 (2.9, 3.9) 3.7 (2.4, 5.6) rwTTNT, months 5.7 (4.9, 6.5) 5.6 (3.7, 7.5)