Dovitinib is an oral, potent inhibitor of FGFR and VEGFR, and can be a promising strategy in patients with recurrent or progressive glioblastoma (GBM).
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.
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.
Dovitinib was not efficacious in prolonging the PFS in patients with recurrent GBM irrespective of prior treatment with anti-angiogenic therapy (including bevacizumab).
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This study was supported by Novartis.
Conflicts of interest
Dr. Ahluwalia’s disclosures are: receipt of grants/research supports: Astrazeneca, Abbvie, BMS, Bayer, Incyte, Pharmacyclics, Novocure, Merck. Receipt of honoraria or consultation fees: Elsevier, Wiley, Astrazeneca, Abvvie, VBI Vaccines, Flatiron, Varian Medical Systems, Prime Education, Bayer; Stock shareholder: Doctible, Mimivax. There are no potential conflicts of interest for other authors.
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Supplementary file3 (JPG 385 kb). Correlation between biomarkers and progression free survival (PFS) a) BMP 9 [<27.0 (blue) vs >27.0 (red)] b) Baseline Endoglin [<250.0 (blue) vs > 250.0 (red)] c) Baseline CD73 [<1.2 (blue) vs >1.2 (red)] d) Baseline TSP 2 [<1800 (blue) vs >1800 (red)] e) Overall Change in TGFβ 2 at Cycle 1 Day 28 f) Overall Change in VEGF R3 at Cycle 1 Day 28. (Blue (-1) =decrease compared to baseline; red (1) =increase)
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Sharma, M., Schilero, C., Peereboom, D.M. et al. Phase II study of Dovitinib in recurrent glioblastoma. J Neurooncol 144, 359–368 (2019). https://doi.org/10.1007/s11060-019-03236-6
- Anti-angiogenic therapy