| 标题 |
Combination BRAF/MEK inhibitors for melanoma with active brain metastases: A real-world multi-center experience
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| 其它 | Melanoma metastatic to the brain remains a treatment challenge. BRAF and MEK kinase inhibitors (BRAF/MEK-I) can elicit rapid responses in BRAF-mutant melanomas, but their clinical develop-ment was largely limited to patients without active/symptomatic brain metastases. We conducted a multi-center retrospective study in real-life patients with melanoma and active brain metastases treated with combination BRAF/MEK-I. Sixty-five patients were included (38 men and 27 women, median age 49). Prior to initiation of BRAF/MEK-I, 44 patients had received another systemic therapy (immunotherapy in 23 cases), 18 had brain surgery, and 40 had brain radiation. LDH was normal in 26 patients, 1-2x elevated in 20, and >2x elevated in 11. For treatment, 53 patients received dabrafenib/trametinib, 10 received vemurafenib/cobimetinib, 1 received encorafenib/binimetinib, and 1 received vemurafenib/trametinib. There were no new treatment-related safety signals in our cohort. Seventeen patients continued on therapy through the cut-off date. After initiation of therapy, steroid dose could be decreased in 20 of 33 patients (10 tapered off entirely), anticon-vulsants were stopped in 4 of 21, and narcotics were stopped in 4 of 12. Median progression-free survival (PFS) from the start of BRAF/MEK-I was 5.3 months (95% CI 3.6-6.1), and median overall survival (OS) was 9.5 months (95% CI: 7.7-13.5). Twenty patients were surviving at the cut-off date. Univariate analysis of age, sex, ulceration status, thickness, stage, location, or LDH did not reveal significant predictors of PFS or OS within our cohort. We conclude that besides immunotherapy, combination therapy with BRAF/MEK inhibitors is a viable option for the treatment of patients with BRAF-mutant melanoma and brain metastases. However, further studies are needed to define the optimal clinical approach in this population. |
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