CTIM-02. TWO OUNCES OF PREVENTION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF VEGF AND IMMUNE CHECK POINT INHIBITION FOR PRIMARY AND SECONDARY PREVENTION OF BRAIN METASTASES

Abstract INTRODUCTION As treatments for cancer outside of the central nervous system improve, brain metastases (BMs) are becoming increasingly frequent. Despite novel treatment options, BMs remain a frequent cause of death for many advanced malignancies, and both the metastases and their treatments are associated with profound cognitive, quality of life, and economic costs. METHODS We conducted exhaustive, PRISMA-compliant systematic reviews of the literature from January 2000 to June 2020 for studies comparing the frequency of new BM in patients treated with chemotherapy regimens including and not including bevacizumab (“primary prevention”), and for studies comparing the frequency of new outside-of-treatment-field metastases in patients treated with stereotactic radiosurgery (SRS) with or without immune checkpoint inhibitors (“secondary prevention”). Pre-specified data was extracted and summary statistics were calculated using the inverse variance method and random effects model. RESULTS Seven studies (n=6,212) reported on BMs in breast, lung, and colon cancer patients treated with chemotherapy with or without bevacizumab. The relative risk (RR) and 95% confidence intervals [95% CI] for the development of new brain metastases was 0.71 [0.55–0.91, p=0.001]. A sensitivity analysis performed on the 3 breast cancer trials (n=2,350) showed a RR of 0.57 [0.34–0.94, p=0.027]. Seven studies (n=609) reported on patients with melanoma BM receiving SRS without or without an ICI. The RR for the development of new out-of-treatment field brain metastases was 0.70 [0.51–0.94, p=0.017]. Results were similar in sensitivity analyses examining only class I and class II trials. CONCLUSION This analysis suggests that the addition of bevacizumab to chemotherapy or ICI SRS+/- chemotherapy can reduce the development of first-ever or new BM by 30% in patients with advanced stage breast, lung, or colon cancer. Prospective trials of primary and secondary prevention in patient groups at high risk of developing BMs, and examining additional predictors of response, are currently underway.