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

Liao, Guixiang1; Fu, Yuxiang1; Arooj, Sumbal1,2; Khan, Muhammad1,3; Li, Xianming1; Yan, Maosheng1; Li, Zihuang1; Yang, Hongli1; Zheng, Tao1; Xu, Ruilian1

2022-06-24

10.3389/fonc.2022.704890

Frontiers in Oncology   Impact Factor & Quartile

2234-943X

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 Registrationhttps://www.crd.york.ac.uk/prospero/), identifier CRD42020185984.

MEK inhibitors BRAF inhibitors previous therapy prognosis melanoma brain metastasis

SCI

English

First ; Corresponding

Natural Science Foundation of Shenzhen[JCYJ20170307095828424] ; Shenzhen Health and Family Planning System Research Project[SZBC2017024] ; Technical Research and Cultivation Project for the Youth of Shenzhen Peoples Hospital[SYKYPY2019029]

Oncology

Oncology

WOS:000822676900001

FRONTIERS MEDIA SA

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Dept Radiat Oncol, Shenzhen, Peoples R China
2.Univ Sialkot, Dept Biochem & Mol Biol, Sialkot, Pakistan
3.Anhui Med Univ, Affiliated Hosp 1, Dept Oncol, Hefei, Peoples R China

Liao, Guixiang,Fu, Yuxiang,Arooj, Sumbal,et al. 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[J]. Frontiers in Oncology,2022,12.

Liao, Guixiang.,Fu, Yuxiang.,Arooj, Sumbal.,Khan, Muhammad.,Li, Xianming.,...&Xu, Ruilian.(2022).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.Frontiers in Oncology,12.

Liao, Guixiang,et al."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".Frontiers in Oncology 12(2022).