Phase II study of Dovitinib in recurrent glioblastoma.

Journal Article

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).

Full Text

Duke Authors

Cited Authors

  • Sharma, M; Schilero, C; Peereboom, DM; Hobbs, BP; Elson, P; Stevens, GHJ; McCrae, K; Nixon, AB; Ahluwalia, MS

Published Date

  • September 2019

Published In

Volume / Issue

  • 144 / 2

Start / End Page

  • 359 - 368

PubMed ID

  • 31292802

Pubmed Central ID

  • 31292802

Electronic International Standard Serial Number (EISSN)

  • 1573-7373

Digital Object Identifier (DOI)

  • 10.1007/s11060-019-03236-6

Language

  • eng

Conference Location

  • United States