Peri-radiosurgical administration of bevacizumab improves radiographic response to single and fractionated stereotactic radiosurgery for large brain metastasis

Introduction Stereotactic radiosurgery (SRS) is a standard of care for brain metastases (BM) patients, yet large BM are at a greater risk for radionecrosis and local progression (LP). Concomitant bevacizumab and radiotherapy has been shown to improve outcomes in primary and metastatic brain tumors. This retrospective study investigated the efficacy and safety of concurrent bevacizumab and SRS for large BM. Methods From 2015 to 2019, patients with a BM diameter ≥ 2 cm who received either combination therapy (n = 49, SRS + BVZ group), or SRS alone (n = 73, SRS group) were enrolled. Bevacizumab was given peri-radiosurgically with a 2-week interval. Radiographic response was assessed using the RECIST version 1.1. Competing risk and logistic regression analysis were performed to evaluate prognostic factors. Results Radiographic response was achieved in 41 patients (84%) in the SRS + BVZ group and 37 patients (51%) in the SRS group (p = 0.001). In the multivariate regression analysis, concurrent bevacizumab was independently associated with a better radiographic response (p = 0.003). The cumulative incidences of LP and ≥ grade 2 radionecrosis at 12 months between the SRS + BVZ group and SRS group were 2% versus 6.8%, and 14.3% versus 14.6%, respectively. For patients with BM size ≥ 3 cm, the cumulative incidence of LP was significantly lower in the SRS + BVZ group (p = 0.03). No ≥ grade 4 toxicity was observed in either group. Conclusions Concurrent bevacizumab and SRS for large BM is highly effective, with a better radiographic response and minimal excessive treatment-related toxicities. Peri-radiosurgical bevacizumab preferentially reduced the risk of LP, especially for BM size ≥ 3 cm.