文摘

Bevacizumab is FDA-approved for patients with recurrent GBM. However, the median duration of response is only 4?months. Potential mechanisms of resistance include upregulated FGF signaling and increased PDGF-mediated pericyte coverage. Nintedanib is an oral, small-molecule tyrosine kinase inhibitor of PDGFR α/β, FGFR 1-3, and VEGFR 1-3 that may overcome resistance to anti-VEGF therapy. This was a two-stage phase II trial in adults with first or second recurrence of GBM, stratified by prior bevacizumab therapy (ClinicalTrials.gov number NCT01380782; 1199.94). The primary endpoint was PFS6 in the bevacizumab-naive arm (Arm A) and PFS3 in the post-bevacizumab arm (Arm B). Up to 10 anaplastic glioma (AG) patients were accrued to each arm in exploratory cohorts. Twenty-two patients enrolled in Arm A and 14 in Arm B. Arm A included 12 GBMs (55?%), 13 patients with one prior regimen (59?%), and median age 54?years (range 28-5). Arm B included 10 GBMs (71?%), one patient with one prior regimen (7?%), and median age 52?years (range 32-0). Median KPS overall was 90 (range 60-00). There were no responses. In Arm A (GBM only), PFS6 was 0?%, median PFS 28?days (95?% CI 27-3), and median OS 6.9?months (3.7-.1). In Arm B (GBM only), PFS3 was 0?%, median PFS 28?days (22-8), and median OS 2.6?months (1.0-.9). Among AG patients in each arm, PFS6 was 0?%. Treatment was well tolerated. In conclusion, nintedanib is not active against recurrent high-grade glioma, regardless of prior bevacizumab therapy.