Pazopanib in advanced soft tissue sarcomas.
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Embargo End Date
ICR Authors
Authors
Lee, ATJ
Jones, RL
Huang, PH
Jones, RL
Huang, PH
Document Type
Journal Article
Date
2019-05-17
Date Accepted
2019-04-16
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.
Citation
Signal transduction and targeted therapy, 2019, 4 pp. 16 - ?
Source Title
Publisher
NATURE PUBLISHING GROUP
ISSN
2095-9907
eISSN
2059-3635
Collections
Research Team
Sarcoma Clinical Trials (R Jones)
Molecular and Systems Oncology
Molecular and Systems Oncology