Pazopanib in advanced soft tissue sarcomas  

作　　者：Alex T.J.Lee Robin L.Jones Paul H.Huang 

机构地区：[1]Division of Molecular Pathology,The Institute of Cancer Research,London,UK [2]Sarcoma Unit,The Royal Marsden NHS Foundation Trust,London,UK [3]Division of Clinical Studies,Institute of Cancer Research,London,UK

出　　处：《Signal Transduction and Targeted Therapy》2019年第1期538-547,共10页信号转导与靶向治疗（英文）

摘　　要：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.

关 键 词：SARCOMA CLINICAL APPROVAL 

分 类 号：R97[医药卫生—药品]