AUTHOR=Liao Guixiang , Fu Yuxiang , Arooj Sumbal , Khan Muhammad , Li Xianming , Yan Maosheng , Li Zihuang , Yang Hongli , Zheng Tao , Xu Ruilian 

TITLE=Impact of Previous Local Treatment for Brain Metastases on Response to Molecular Targeted Therapy in BRAF-Mutant Melanoma Brain Metastasis: A Systematic Review and Meta-Analysis

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.704890

DOI=10.3389/fonc.2022.704890

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Melanoma brain metastases (BMs) are associated with poor prognosis and are the main cause of mortality in melanoma patients. BRAF inhibitors have shown intracranial activity in both treatment-naïve and previously treated BM patients. We aimed to investigate if there was any difference in response of BRAF inhibitors in these two cohorts.</p></sec><sec><title>Materials and Methods</title><p>Electronic database search included PubMed, Medline, and Cochrane library until March 2021 for studies with desired comparative outcomes. Outcomes of interest that were obtained for meta-analysis included intracranial response rate as the primary outcome and survival and safety outcomes as the secondary outcomes. Review Manager version 5.4 was used for data analysis.</p></sec><sec><title>Results</title><p>Three studies comprising 410 BRAF-mutated melanoma patients with BMs were included according to eligibility criteria. The comparative cohort included patients with treatment-naïve BMs (TN cohort; <italic>n</italic> = 255) and those who had progressive disease after receiving local brain treatment for BMs (PT cohort; <italic>n</italic> = 155). Meta-analysis revealed that BRAF inhibitors (vemurafenib and dabrafenib) and BRAF/MEK inhibitor combination (dabrafenib and trametinib) induced significantly higher intracranial disease control (OR 0.58 [95% CI: 0.34, 0.97], <italic>p</italic> = 0.04) and a trend toward improved progression-free survival (PFS) (HR 1.22 [95% CI: 0.98, 1.52], <italic>p</italic> = 0.08) in the PT cohort as compared to the TN cohort. Overall survival was not significantly different between the cohorts (HR 1.16 [95% CI: 0.89, 1.51], <italic>p</italic> = 0.28). Subgroup analysis revealed that PFS was significantly improved (HR 1.67 [95% CI: 1.06, 2.62], <italic>p</italic> = 0.03), and a trend toward improved OS (HR 1.62 [95% CI: 0.95, 2.75], <italic>p</italic> = 0.08) was achieved in patients receiving BRAF/MEK inhibitor combination and patients with BRAFv600K mutation receiving dabrafenib alone. No increase in overall adverse events (AEs), grade 3/4 AEs, and severe adverse events (SAEs) was observed between the cohorts.</p></sec><sec><title>Conclusions</title><p>BRAF inhibitors (plus MEK inhibitor) may achieve better intracranial disease stability in BRAF-mutant melanoma patients who have received previous local treatment for BMs.</p></sec><sec><title>Systematic Review Registration</title><p><uri xlink:href="https://www.crd.york.ac.uk/prospero/" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.crd.york.ac.uk/prospero/</uri>), identifier CRD42020185984.</p></sec>