Pazopanib is approved by the FDA and EMA as targeted therapy for the indication of advanced
renal cell carcinoma (RCC). Hepatic safety events were observed in the pazopanib pivotal
clinical trial and the U.S. pazopanib label information contains a 'black box warning'
regarding hepatotoxicity. These clinical observations have prompted GSK to undertake a
proactive pharmacovigilance strategy focused on hepatic safety that goes beyond spontaneous
reporting of adverse events.
The goals of the study are to assess prescriber compliance with pazopanib label guidelines
for liver monitoring among patients with RCC, as well as to quantify and characterize the
hepatic safety profile of the product in real-world clinical practice compared to other
anti-vascular endothelial growth factor (anti-VEGF) drugs. As part of regulatory commitments,
GSK will conduct parallel epidemiologic analyses in different patient populations as
represented in multiple databases of electronic medical records. To enhance accrual of data,
GSK will conduct this safety surveillance program simultaneously across datasets in order to
detect and characterize all cases of liver enzyme elevations in diverse populations of
patients receiving pazopanib. Two additional goals of this study are to evaluate the
incidence of cases of combinations of liver enzyme elevations indicative of Hy's Law and
drug-induced acute liver failure among users of pazopanib compared to users of other
anti-VEGF drugs. This research effort will be coordinated by an external coordinating center.
An epidemiologic cohort study design, nested in several databases of electronic medical
information, will be employed for the research questions. Following the availability of
pazopanib in the relevant medical care system, the study will collect retrospective data at
regular intervals over the course of four years among persons exposed to pazopanib and other
anti-VEGF agents. Each patient will be characterized based on additional available
information in the database (e.g., demographics, concomitant medications). Elevations in
liver enzymes will be identified through laboratory data captured in these databases.
Potential Hy's Law and acute liver failure cases will be identified through established
screening criteria, and screen-positive cases will be reviewed by an adjudication committee
of hepatologists for final determination of drug-associated causality.