Abstract

Pazopanib is the first and only tyrosine kinase inhibitor currently approved for the treatment of multiple histological subtypes of soft tissue sarcoma (STS). Initially developed as a small molecule inhibitor of vascular endothelial growth factor receptors, preclinical work indicates that pazopanib exerts an anticancer effect through the inhibition of both angiogenic and oncogenic signaling pathways. Following the establishment of optimal dosing and safety profiles in early phase studies and approval for the treatment of advanced renal cell carcinoma, pazopanib was investigated in STS. A landmark phase III randomized study demonstrated improved progression-free survival with pazopanib compared to that with placebo in pretreated patients with STS of various subtypes. The efficacy of pazopanib in specific STS subtypes has been further described in real-world-based case series in both mixed and subtype-specific STS cohorts. At present, there are no clinically validated predictive biomarkers for use in selecting patients with advanced STS for pazopanib therapy, limiting the clinical effectiveness and cost-effectiveness of the drug. In this review, we summarize the preclinical and clinical data for pazopanib, outline the evidence base for its effect in STS and explore reported studies that have investigated putative biomarkers.

Details

Title
Pazopanib in advanced soft tissue sarcomas
Author
Lee Alex T J 1 ; Jones, Robin L 2 ; Huang, Paul H 3 

 The Institute of Cancer Research, Division of Molecular Pathology, London, UK (GRID:grid.18886.3f) (ISNI:0000 0001 1271 4623); The Royal Marsden NHS Foundation Trust, Sarcoma Unit, London, UK (GRID:grid.5072.0) (ISNI:0000 0001 0304 893X) 
 The Royal Marsden NHS Foundation Trust, Sarcoma Unit, London, UK (GRID:grid.5072.0) (ISNI:0000 0001 0304 893X); Institute of Cancer Research, Division of Clinical Studies, London, UK (GRID:grid.18886.3f) (ISNI:0000 0001 1271 4623) 
 The Institute of Cancer Research, Division of Molecular Pathology, London, UK (GRID:grid.18886.3f) (ISNI:0000 0001 1271 4623) 
Publication year
2019
Publication date
2019
Publisher
Nature Publishing Group
ISSN
20959907
e-ISSN
20593635
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2226429251
Copyright
© The Author(s) 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.