Phase II study of Dovitinib in recurrent glioblastoma

• Published in: Journal of neuro-oncology Vol. 144; no. 2; pp. 359 - 368
• Main Authors: Sharma, Mayur, Schilero, Cathy, Peereboom, David M., Hobbs, Brian P., Elson, Paul, Stevens, Glen H. J., McCrae, Keith, Nixon, Andrew B., Ahluwalia, Manmeet S.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2019; Springer Nature B.V
• Subjects: Adult; Aged; Angiogenesis; Benzimidazoles - therapeutic use; Bevacizumab; Biomarkers, Tumor - analysis; Brain cancer; Brain Neoplasms - drug therapy; Brain Neoplasms - pathology; Clinical Study; Female; Fibroblast growth factor receptors; Follow-Up Studies; Glioblastoma; Glioblastoma - drug therapy; Glioblastoma - pathology; Humans; Immunotherapy; Male; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Neurology; Oncology; Prognosis; Prospective Studies; Quinolones - therapeutic use; Survival; Survival Rate; Targeted cancer therapy; Toxicity; Vascular endothelial growth factor receptors; Anti-angiogenic therapy; Recurrent; Dovitinib; Glioblastoma; Bevacizumab
• ISSN: 0167-594X; 1573-7373; 1573-7373
• DOI: 10.1007/s11060-019-03236-6

Introduction Dovitinib is an oral, potent inhibitor of FGFR and VEGFR, and can be a promising strategy in patients with recurrent or progressive glioblastoma (GBM). Methods This was an open label phase II study of two arms: Arm 1 included anti-angiogenic naïve patients with recurrent GBM and Arm 2 included patients with recurrent GBM that had progressed on prior anti-angiogenic therapy. Nineteen subjects were enrolled in Arm 1 and 14 subjects in Arm 2. The primary endpoint was 6-month progression-free survival (PFS-6) in Arm 1 and time to progression (TTP) in Arm 2. The secondary endpoints were toxicity, objective response rate (ORR) and overall survival. Results Patients in Arm 2 (compared to Arm 1) tended to have longer intervals from diagnosis to study entry (median 26.9 vs. 8.9 months, p = 0.002), experienced more recurrences (64%, had 3–4 prior recurrences compared to 0, p < 0.0001) and tended to be heavily pretreated (71% vs. 26–32% p = 0.04 or 0.02). 6-month PFS was 12% ± 6% for the Arm 1 and 0% for Arm 2. TTP was similar in both treatment arms (median 1.8 months Arm 1 and 0.7–1.8 months Arm 2, p = 0.36). Five patients (15%) had grade 4 toxicities and 22 patients (67%) had grade 3 toxicities. There were no significant differences between the two arms with respect to the amount of change in the levels of biomarkers from baseline. Conclusion Dovitinib was not efficacious in prolonging the PFS in patients with recurrent GBM irrespective of prior treatment with anti-angiogenic therapy (including bevacizumab).