In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. TPS2104-TPS2104
Kurzfassung:
TPS2104 Background: Bevacizumab is the standard of care for patients with recurrent high-grade glioma (HGG). However, with current treatment options the median duration of response is only approximately 4 months. Potential mechanisms of resistance include upregulation of fibroblast growth factor (FGF) and increased pericyte coverage mediated by platelet-derived growth factor (PDGF). Nintedanibis an oral, small-molecule tyrosine kinase inhibitor of PDGFR α/β, FGFR 1/3, and vascular endothelial growth factor receptor (VEGFR) 1-3 that may overcome the problem of resistance to prior anti-VEGF therapy. Methods: This is an open-label, phase II trial in adults with first or second recurrence of HGG, stratified by prior therapy with bevacizumab. The primary endpoint is 6-month progression-free survival (PFS6) in the bevacizumab-naive arm and PFS3 in the post-bevacizumab arm. A Simon two-stage design is employed. Although the glioblastoma (GBM) comparison is the one of primary concern, 10 anaplastic glioma (AG) participants will be accrued to each arm in exploratory cohorts. Results: Nine of 40 GBM patients and 10 of 10 AG patients have been accrued in the bevacizumab-naive arm. Data in this arm are maturing. In the post-bevacizumab arm, 14 patients have been accrued, 10 of whom had GBM (71%). There were 11 men (79%), median age was 52 years (range 32-70), and median KPS was 90 (range, 60-100). One patient with anaplastic astrocytoma was not evaluable for response analysis because of early withdrawal of consent. There have been no responses. Two patients (1 with GBM and 1 with anaplastic oligodendroglioma) achieved stable disease. Median PFS was 28 days (95% CI: 27-28), and maximum PFS was 56 days. Median OS was 57 days (95% CI: 29-155). The post-bevacizumab arm was stopped after stage 1. Treatment was well tolerated, with limited Grade 3 liver function test abnormalities (n = 3), abdominal pain (n = 1), and hypertension (n = 1). Grade 1-2 adverse events also included diarrhea, nausea/vomiting, fatigue, and bleeding. Conclusions: Despite limited toxicity, nintedanibis ineffective in the cohort of recurrent HGG patients who failed bevacizumab. Updated results in the bevacizumab-naive arm will be presented. Clinical trial information: NCT01380782.
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.15_suppl.tps2104
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2013
ZDB Id:
2005181-5
