Combination of metronomic oral pazopanib and topotecan for recurrent glioblastoma with and without previous bevacizumab: Results from a phase 2 clinical trial
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: Background: Glioblastoma (GBM) has limited effective salvage therapy options. The combination of the Type 1B topoisomerase/HIF1α inhibitor topotecan and the tyrosine kinase inhibitor pazopanib has shown promise in solid tumors and may be effective in recurrent GBM. Methods: Patients with recurrent GBM who were bevacizumab-naïve (Group A, 9 patients) or had previous bevacizumab (BEV) (Group B, 22 patients) started daily oral pazopanib (600 mg) and topotecan (0.25 mg). The primary objective was progression-free survival (PFS) at 6 months for Group A and 3 months for Group B patients. Secondary objectives included median progression-free and overall survival (OS), safety, tolerability, and toxicity as measured by patient-reported outcomes (PROs) and adverse event documentation. Results: Group A enrolled 9 evaluable patients and closed to accrual early when interim primary objectives were not met (PFS-6 11%). Group B enrolled 22 evaluable patients and narrowly met its primary objective (PFS-3 18%). Median PFS and OS endpoints demonstrated equivalent to slight improvement upon historical metrics, respectively. The regimen was tolerable and safe save for high frequency of hypertension, with PROs data showing stability or worsening in parallel with tumor stability or progression, respectively. Conclusions: These findings suggest the regimen is safe and tolerable to GBM patients. The regimen was ineffective in bevacizumab-naïve patients and only narrowly met its predetermined endpoint in patients with prior BEV. These results do not support the combination regimen as tested in this protocol for further investigation in GBM.
Source: Neuro-Oncology Advances
Authors: Byram H Ozer, Adam L Cohen, Howard Colman, Marta Penas-Prado, John de Groot, Monica E Loghin, Edward Pan, Jeffrey J Raizer, Priya Kumthekar, Karen L Fink, Tobias Walbert, Ryan T Merrell, Morris D Groves, Manmeet S Ahluwalia, Jing Wu, Eric C Burton, Elizabeth Vera, Tito Mendoza, Ewa Grajkowska, Kathleen Wall, Jennifer Reyes, Ying Yuan, Terri S Armstrong, Mark R Gilbert
Institutions: National Institutes of Health, National Cancer Institute, Huntsman Cancer Institute, The University of Texas MD Anderson Cancer Center, The University of Texas Southwestern Medical Center, Northwestern University, Baylor College of Medicine, Henry Ford Health, Michigan State University, Endeavor Health, Cleveland Clinic
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,615
OpenAlex ID: W7125810384