Title |
Phase II trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas
|
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Published in |
Journal of Neuro-Oncology, October 2014
|
DOI | 10.1007/s11060-014-1631-y |
Pubmed ID | |
Authors |
Andrew D. Norden, David Schiff, Manmeet S. Ahluwalia, Glenn J. Lesser, Lakshmi Nayak, Eudocia Q. Lee, Mikael L. Rinne, Alona Muzikansky, Jorg Dietrich, Benjamin Purow, Lisa M. Doherty, Debra C. LaFrankie, Julee R. Pulverenti, Jennifer A. Rifenburg, Sandra F. Ruland, Katrina H. Smith, Sarah C. Gaffey, Christine McCluskey, Keith L. Ligon, David A. Reardon, Patrick Y. Wen |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Practitioners (doctors, other healthcare professionals) | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Netherlands | 1 | 2% |
Unknown | 48 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 8 | 16% |
Student > Bachelor | 7 | 14% |
Student > Ph. D. Student | 7 | 14% |
Student > Master | 4 | 8% |
Student > Doctoral Student | 3 | 6% |
Other | 6 | 12% |
Unknown | 14 | 29% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 15 | 31% |
Agricultural and Biological Sciences | 6 | 12% |
Neuroscience | 5 | 10% |
Biochemistry, Genetics and Molecular Biology | 3 | 6% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 4% |
Other | 2 | 4% |
Unknown | 16 | 33% |