Objective:We conducted a systematic review and meta-analysis to investigate the role of VEGF inhibitors and immune checkpoint inhibitors (ICIs) in preventing the development of brain metastasis (BMs).Methods:We searched MEDLINE, EMBASE, Cochrane Database, Google Scholar between January 1, 2000 and June 1, 2020. Included studies were randomized controlled trials (RCTs) of adults with systemic cancer which reported incidence of BMs treated with and without VEGF inhibitors, and observational studies of adults with systemic cancer which reported incidence of BMs treated with and without ICIs (there were no RCTs addressing the ICI question). Pooled relative risks (RR) were computed utilizing a binary random-effects model.Results:A search for VEGF and incidence of new BMs revealed 7 studies (6212 patients with breast, colon and non-small cell lung cancer). Meta-analysis showed a lower incidence of new BMs compared to control (RR 0.71, 95% CI: 0.56-0.89, p=0.003). A search for ICIs and incidence of new BMs yielded 8 studies (732 patients with non-small cell lung cancer or metastatic melanoma) where ICIs were used as an adjunct to radiosurgery. Meta-analysis showed a lower incidence of out-of-treatment-field BMs with ICI inhibitors compared to controls at 1 year (RR 0.65, 95% CI: 0.49-0.88, p=0.005). The overall GRADE score for the evidence evaluating the role of bevacizumab and immune checkpoint inhibitors was high and moderate, respectively.Conclusion:VEGF and immune checkpoint inhibitors may have a role in prophylaxis against brain metastases in patients with solid tumors.
Therapeutic Guidance of Tumor Mutation Burden on Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer: A Systematic Review and Comprehensive Meta-analysis
