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RESIDENT’S CORNER

Vanishing bile duct syndrome associated with pazopanib after progression on pembrolizumab

Ying Yan Zhong¹, Luke McLean², Andrew Buckle^1,2, Shankar Siva², Ben Tran²

1 Sir Peter MacCallum Department of Oncology, Peter MacCallum Cancer Centre, University of Melbourne, Victoria, Australia
2 Department of Oncology, Peter MacCallum Cancer Centre, University of Melbourne, Victoria, Australia
Address correspondence to Dr. Ben Tran, Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne VIC 3000 Australia

Canadian Journal of Urology 2020, 27(4), 10339-10341.

Abstract

Pazopanib, a tyrosine kinase inhibitor, has been a standard first-line treatment for metastatic renal cell carcinoma (mRCC). Recent trials combining pazopanib with programmed cell death protein 1 (PD-1) inhibitors, including pembrolizumab, have shown excessive hepatotoxicity. We report a case of fatal hepatotoxicity from vanishing bile duct syndrome (VBDS) associated with pazopanib treatment, in a patient previously exposed to pembrolizumab. This is the first report of pazopanibinduced VBDS. We postulate whether prior exposure to pembrolizumab predisposed towards pazopanib-induction of VBDS, and discuss potential risks of sequential PD-1 inhibitor followed by pazopanib in mRCC, due to prolonged half-lives of PD-1 inhibitors.

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