Antitumor Response of VEGFR2- and VEGFR3-Amplified Angiosarcoma to Pazopanib.

Autor: Ravi V; The University of Texas MD Anderson Cancer Center, Houston, Texas, Sanford EM; Foundation Medicine, Inc., Cambridge, Massachusetts, Wang WL; The University of Texas MD Anderson Cancer Center, Houston, Texas, Ross JS; Foundation Medicine, Inc., Cambridge, Massachusetts, Ramesh N; The University of Texas MD Anderson Cancer Center, Houston, Texas, Futreal A; The University of Texas MD Anderson Cancer Center, Houston, Texas, Patel S; The University of Texas MD Anderson Cancer Center, Houston, Texas, Stephens PJ; Foundation Medicine, Inc., Cambridge, Massachusetts, Miller VA; Foundation Medicine, Inc., Cambridge, Massachusetts, Ali SM; Foundation Medicine, Inc., Cambridge, Massachusetts
Jazyk: angličtina
Zdroj: Journal of the National Comprehensive Cancer Network : JNCCN [J Natl Compr Canc Netw] 2016 May; Vol. 14 (5), pp. 499-502.
DOI: 10.6004/jnccn.2016.0058
Abstrakt: Background: Angiosarcoma is a malignant neoplastic disease originating from or differentiating toward vascular endothelium, for which systemic pharmacologic treatment has limited durability. The molecular oncogenesis of angiosarcoma is often linked to inappropriate activations of vascular endothelial growth factor receptor (VEGFR) family members, which presents an opportunity for the use of therapy that selectively targets the machinery of vascular signaling.
Methods: Hybridization capture of 3,320 exons of 182 cancer-related genes and the introns of 14 genes frequently rearranged in cancer was applied to more than 50 ng of DNA extracted from a formalin-fixed, paraffin-embedded biopsy of recurrent angiosarcoma and was sequenced to high, uniform coverage of 939x.
Results: The angiosarcoma harbored amplifications of VEGFR2 (KDR) of 8 copies and VEGFR3 (FLT4) of 16 copies. The patient was initially treated with sorafenib, an inhibitor of VEGFR2, and developed progressive disease. The patient then received pazopanib, an inhibitor of VEGFR2 and VEGFR3 and experienced a potent antitumor response resulting in clinically stable disease for 6 months.
Conclusions: This exceptional response to pazopanib treatment suggests that a subset of patients with angiosarcoma with genomic alterations in vascular signaling genes may respond well to pazopanib.
(Copyright © 2016 by the National Comprehensive Cancer Network.)
Databáze: MEDLINE