Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, 9500 Euclid Ave, S73, Cleveland, OH, 44195, USA.
Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
J Neurooncol. 2019 Sep;144(2):359-368. doi: 10.1007/s11060-019-03236-6. Epub 2019 Jul 11.
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).
多韦替尼是一种口服、强效的 FGFR 和 VEGFR 抑制剂，在复发性或进展性胶质母细胞瘤（GBM）患者中可能是一种有前途的治疗策略。
这是一项开放标签的 2 期研究，包括两个队列：队列 1 纳入复发性 GBM 的抗血管生成初治患者，队列 2 纳入复发性 GBM 患者，这些患者在先前的抗血管生成治疗中进展。队列 1 纳入 19 例患者，队列 2 纳入 14 例患者。主要终点是队列 1 的 6 个月无进展生存期（PFS-6）和队列 2 的疾病进展时间（TTP）。次要终点是毒性、客观缓解率（ORR）和总生存期。
队列 2（与队列 1 相比）的患者从诊断到入组的间隔时间较长（中位数分别为 26.9 个月和 8.9 个月，p=0.002），复发次数更多（64%，有 3-4 次复发，而 0 次，p<0.0001），且预处理程度更高（71%，与 26%-32%相比，p=0.04 或 0.02）。队列 1 的 6 个月 PFS 为 12%±6%，队列 2 为 0%。两个治疗队列的 TTP 相似（队列 1 的中位数为 1.8 个月，队列 2 的中位数为 0.7-1.8 个月，p=0.36）。有 5 例（15%）患者发生 4 级毒性，22 例（67%）患者发生 3 级毒性。两个队列在基线水平的生物标志物水平变化量方面没有显著差异。
多韦替尼在延长复发性 GBM 患者的 PFS 方面无效，无论患者是否先前接受过抗血管生成治疗（包括贝伐珠单抗）。
