Safety and Efficacy of Hypofractionated Stereotactic Radiotherapy with Anlotinib Targeted Therapy for Glioblastoma at First Recurrence: A Preliminary Report

Background: The optimal treatment for recurrent glioblastoma (rGBM) remains uncertain. Hypofractionated stereotactic radiotherapy (HSRT) and anti-vascular endothelial growth factor (VEGF) antibodies (e.g., bevacizumab) have been reported to have a promising survival benefit and acceptable toxicity in recent studies. Anlotinib is a new orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR) and c-kit. It has dual anti-angiogenic and anti-tumour growth effects. This preliminary study describes our initial experience with HSRT and anlotinib as a salvage treatment for rGBM.MethodsBetween December 2019 and June 2020, rGBM patients treated with HSRT using CyberKnife concurrently with anlotinib were retrospectively analysed. Anlotinib was prescribed at 12 mg daily during HSRT. Adjuvant anlotinib was administered at 12 mg d1-14 every 3 weeks. The primary endpoint was the objective response rate (ORR) determined by the treating investigators using the Response Assessment in Neuro-Oncology (RANO) criteria, and secondary endpoints included overall survival (OS), progression-free survival (PFS) after salvage treatment, and toxicity. Toxicity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) 5.0.ResultsWe retrospectively reviewed five patients who received salvage HSRT and anlotinib for recurrent GBM.The median planning target volume (PTV) was 26.94 cm3 (5.53–54.41 cm3). The prescribed dose was 25.0 Gy in 5 fractions. The median number of cycles of anlotinib was 9 (4–15) cycles. The median baseline Karnofsky Performance Status (KPS) was 80 (70–90). The follow-up ranged from 4 to 10 months. The ORR was 100%. Three (60%) patients had a best outcome of a partial response (PR), and 2 (40%) achieved a complete response (CR). No patients died or had progressive disease (PD) at the last follow-up. Two patients had grade 2 hand-foot syndrome, which was relieved after dermatologic treatments, and no other grade 3 or higher toxicities were recorded.ConclusionsSalvage HSRT combined with anlotinib showed a favourable outcome and acceptable toxicity for rGBM patients in this preliminary report. A prospective phase II study (NCT04197492) is ongoing to further investigate the value of HSRT combined with anlotinib in rGBM.