Efficacy and safety of combining bevacizumab and fractionated stereotactic radiotherapy for extensive brain metastases in patients with non‐small cell lung cancer: a prospective phase II study (GASTO‐1053)

Abstract Background The prognosis for non‐small cell lung cancer (NSCLC) patients with extensive brain metastases (BMs) treated with radiotherapy alone remains poor. Based on the synergistic potential of radiotherapy and angiogenesis inhibitors, we initiated this phase II study to assess the efficacy and safety of combining bevacizumab (Bev) with fractionated stereotactic radiotherapy (FSRT) in managing extensive BMs in NSCLC patients who had stable extracranial disease. Methods Patients with extensive BMs from NSCLC, deemed unsuitable for stereotactic radiosurgery, were prospectively enrolled following multidisciplinary tumor board evaluation. Patients received FSRT (40 Gy in 10 fractions or 30 Gy in 5 fractions) in combination with Bev (7.5 mg/kg on day 1 prior to FSRT and on day 21 post‐FSRT). The primary endpoint was intracranial progression‐free survival (IPFS). Secondary endpoints included overall survival, progression‐free survival, quality of life (QOL), and toxicities. For comparison, NSCLC patients with extensive BMs treated with whole‐brain radiotherapy (WBRT) plus FSRT or FSRT alone were matched 1:1 with the study group (Bev + FSRT) using the propensity score matching. Results One hundred and six patients were included in the Bev + FSRT group, with a median follow‐up duration of 35.8 months. The median IPFS was 18.3 months (95% confidence interval, 15.2‐23.3 months). The Bev + FSRT group showed a significant improvement in IPFS compared to both the WBRT + FSRT group (9.6 months, P < 0.001) and the FSRT alone group (8.9 months, P < 0.001). Treatment was well tolerated, with grade 1 radiation necrosis in 1 patient. Bev + FSRT treatment significantly reduced tumor volume ( P < 0.001), peritumoral edema volume ( P = 0.004), and vascular leakage ( P < 0.001). Furthermore, QOL was significantly improved after Bev + FSRT treatment, particularly in patients with symptomatic extensive BMs. Conclusion These findings support the combination of Bev and FSRT as a safe and effective treatment strategy for extensive BMs in NSCLC patients, offering improved intracranial disease control and symptom relief while avoiding the neurotoxicity associated with WBRT. A randomized trial is warranted to validate the findings of the current study. Trial registration ClinicalTrials.gov, NCT04345146. Registration date: 2020‐02‐22.