Safety and Efficacy of CyberKnife Radiosurgery Plus Anlotinib Hydrochloride in Patients with Recurrent Glioblastoma: A Prospective Phase II Single-Arm Study.

2050 Background: Glioblastoma (GBM) is a tumor known for its highly vascular nature and limited treatment options upon disease recurrence. While Bevacizumab which target VEGF-A has gained approval for treating recurrent glioblastoma, the multi-target tyrosine kinase inhibitor Anlotinib has the ability to directly target Vascular Endothelial Growth Factor Receptor (VEGFR), Platelet-Derived Growth Factor Receptor (PDGFR), and Fibroblast Growth Factor Receptor (FGFR). Theoretically, its anti-angiogenic effect may exceed that of Bevacizumab, and preliminary studies have shown its therapeutic efficacy in recurrent GBM (rGBM), indicating promising treatment potential. This study aims to present findings regarding the effectiveness and safety of combining Anlotinib with stereotactic radiosurgery (SRS) in treating patients with rGBM. Methods: Patients who underwent surgery, standard radiotherapy, and temozolomide chemotherapy and were diagnosed with recurrence based on Response Assessment in Neuro-Oncology (RANO) criteria and/or biopsy were eligible for inclusion. Each patient underwent CyberKnife SRS (25Gy/5fx) in combination with oral administration of Anlotinib (12 mg, daily, days 1–14/3 weeks) until encountering disease progression or experiencing intolerable adverse effects. The primary objective was the investigator-assessed median overall survival (OS) using the Response Assessment in Neuro-Oncology (RANO) criteria. Results: Between December 2019 and July 2023, 22 patients (median age: 55 years; range: 28–70) were included. According to RANO criteria, 21 patients exhibited tumor response, with 6 achieving complete response, resulting in an objective response rate of 95.5%. Additionally, one patient maintained stable disease without progression. Median progression-free survival (PFS) was 9.1 months (95% CI, 7.5–24.7), with a 6-month PFS rate of 85.7% (95% CI, 71.9–100.0). Median overall survival was 19.5 months (95% CI, 10.6–46.8). Common adverse events included hand-foot skin reactions (40.9%), hypercholesterolemia (27.3%), and hypertension (22.7%). Four patients experienced grade 3 adverse events, accounting for an 18.2% incidence rate. Therapy discontinuation due to ischemic stroke (grade 3) occurred in one patient. No grade 4 events or treatment-related deaths were reported. Conclusions: The combination of salvage SRS with Anlotinib demonstrated promising outcomes and manageable toxicity in managing recurrent GBM. Currently, a phase II randomized controlled trial, supported by the Shanghai Municipal Commission of Health, is underway. This trial aims to compare the efficacy of Anlotinib combined with radiosurgery against Bevacizumab combined with radiosurgery for the treatment of rGBM patients, further exploring this therapeutic regimen. Clinical trial information: NCT04197492 .