PMID- 35814449 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 12 DP - 2022 TI - 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. PG - 704890 LID - 10.3389/fonc.2022.704890 [doi] LID - 704890 AB - BACKGROUND: 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-naive and previously treated BM patients. We aimed to investigate if there was any difference in response of BRAF inhibitors in these two cohorts. MATERIALS AND METHODS: 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. RESULTS: Three studies comprising 410 BRAF-mutated melanoma patients with BMs were included according to eligibility criteria. The comparative cohort included patients with treatment-naive BMs (TN cohort; n = 255) and those who had progressive disease after receiving local brain treatment for BMs (PT cohort; n = 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], p = 0.04) and a trend toward improved progression-free survival (PFS) (HR 1.22 [95% CI: 0.98, 1.52], p = 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], p = 0.28). Subgroup analysis revealed that PFS was significantly improved (HR 1.67 [95% CI: 1.06, 2.62], p = 0.03), and a trend toward improved OS (HR 1.62 [95% CI: 0.95, 2.75], p = 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. CONCLUSIONS: BRAF inhibitors (plus MEK inhibitor) may achieve better intracranial disease stability in BRAF-mutant melanoma patients who have received previous local treatment for BMs. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/), identifier CRD42020185984. CI - Copyright (c) 2022 Liao, Fu, Arooj, Khan, Li, Yan, Li, Yang, Zheng and Xu. FAU - Liao, Guixiang AU - Liao G AD - Department of Radiation Oncology, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China. FAU - Fu, Yuxiang AU - Fu Y AD - Department of Radiation Oncology, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China. FAU - Arooj, Sumbal AU - Arooj S AD - Department of Radiation Oncology, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China. AD - Department of Biochemistry and Molecular Biology, University of Sialkot, Sialkot, Pakistan. FAU - Khan, Muhammad AU - Khan M AD - Department of Radiation Oncology, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China. AD - Department of Oncology, First Affiliated Hospital of Anhui Medical University, Hefei, China. FAU - Li, Xianming AU - Li X AD - Department of Radiation Oncology, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China. FAU - Yan, Maosheng AU - Yan M AD - Department of Radiation Oncology, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China. FAU - Li, Zihuang AU - Li Z AD - Department of Radiation Oncology, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China. FAU - Yang, Hongli AU - Yang H AD - Department of Radiation Oncology, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China. FAU - Zheng, Tao AU - Zheng T AD - Department of Radiation Oncology, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China. FAU - Xu, Ruilian AU - Xu R AD - Department of Radiation Oncology, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China. LA - eng PT - Systematic Review DEP - 20220624 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC9263360 OTO - NOTNLM OT - BRAF inhibitors OT - MEK inhibitors OT - melanoma brain metastasis OT - previous therapy OT - prognosis COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/07/12 06:00 MHDA- 2022/07/12 06:01 PMCR- 2022/01/01 CRDT- 2022/07/11 04:17 PHST- 2021/07/27 00:00 [received] PHST- 2022/04/25 00:00 [accepted] PHST- 2022/07/11 04:17 [entrez] PHST- 2022/07/12 06:00 [pubmed] PHST- 2022/07/12 06:01 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2022.704890 [doi] PST - epublish SO - Front Oncol. 2022 Jun 24;12:704890. doi: 10.3389/fonc.2022.704890. eCollection 2022.