Pazopanib received US Food and Drug Administration approval in 2009 for advanced renal cell carcinoma. During clinical development, liver chemistry abnormalities and adverse hepatic events were observed, leading to a boxed warning for hepatotoxicity and detailed label prescriber guidelines for liver monitoring. As part of postapproval regulatory commitments, a cohort study was conducted to assess prescriber compliance with liver monitoring guidelines.
Over a 4-year period, a distributed network approach was used across 3 databases: US Veterans Affairs Healthcare System, a US outpatient oncology community practice database, and the Dutch PHARMO Database Network. Measures of prescriber compliance were designed using the original pazopanib label guidelines for liver monitoring.
Results from the VA (n = 288) and oncology databases (n = 283) indicate that prescriber liver chemistry monitoring was less than 100%: 73% to 74% compliance with baseline testing and 37% to 39% compliance with testing every 4 weeks. Compliance was highest near drug initiation and decreased over time. Among patients who should have had weekly testing, the compliance was 56% in both databases. The more serious elevations examined, including combinations of liver enzyme elevations meeting the laboratory definition of Hy’s law were infrequent but always led to appropriate discontinuation of pazopanib. Only 4 patients were identified for analysis in the Dutch database; none had recorded baseline testing.
In this population-based study, prescriber compliance was reasonable near pazopanib initiation but low during subsequent weeks of treatment. This study provides information from real-world community practice settings and offers feedback to regulators on the effectiveness of label monitoring guidelines.
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From *Worldwide Epidemiology, Research and Development, GlaxoSmithKline, Singapore; †Evidera, Lexington; ‡Biogen, Cambridge; §Harvard University; MAVERIC and GRECC, Boston Veterans Affairs Healthcare Administration, Boston, Massachusetts; ∥PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands; ¶Evidera, Lexington; #MAVERIC, Boston Veterans Affairs Healthcare Administration, Boston; **Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts; ††Global Clinical Safety and Reporting, Research and Development, GlaxoSmithKline; and ‡‡Research and Development, GlaxoSmithKline, Collegeville, Pennsylvania.
Correspondence: Sumitra Shantakumar, PhD, Worldwide Epidemiology, Asia Pacific and North Asia, Research and Development, GlaxoSmithKline, 150 Beach Road, 26-00 Gateway West, Singapore (e-mail: firstname.lastname@example.org).
Disclosure of Potential Conflicts of Interest: S.S. and J.J.N. were employees and owned stock in GlaxoSmithKline at the time that the study was designed and executed. M.P.P.v.H.-S. is an employee of the PHARMO Institute. This independent research institute performs financially supported studies for government and related health-care authorities and several pharmaceutical companies. B.L.N. is an employee of Evidera, which received funding from GSK for this study. S.A.H. was an employee of New England Research Institutes, which received funding from GSK for this study.
This study was funded by GlaxoSmithKline.