Reference Detail

Ref Type Journal Article
PMID (25338318)
Authors Norden AD, Schiff D, Ahluwalia MS, Lesser GJ, Nayak L, Lee EQ, Rinne ML, Muzikansky A, Dietrich J, Purow B, Doherty LM, LaFrankie DC, Pulverenti JR, Rifenburg JA, Ruland SF, Smith KH, Gaffey SC, McCluskey C, Ligon KL, Reardon DA, Wen PY
Title Phase II trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas.
Journal Journal of neuro-oncology
Vol 121
Issue 2
Date 2015 Jan
URL
Abstract Text 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 28-75). Arm B included 10 GBMs (71 %), one patient with one prior regimen (7 %), and median age 52 years (range 32-70). Median KPS overall was 90 (range 60-100). There were no responses. In Arm A (GBM only), PFS6 was 0 %, median PFS 28 days (95 % CI 27-83), and median OS 6.9 months (3.7-8.1). In Arm B (GBM only), PFS3 was 0 %, median PFS 28 days (22-28), and median OS 2.6 months (1.0-6.9). 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown brain glioma not applicable Nintedanib Phase II Actionable In a Phase II clinical trial, Ofev (nintedanib) failed to show any efficacy in patients with recurrent high-grade glioma, regardless of prior bevacizumab therapy (PMID: 25338318). 25338318