Vanishing bile duct syndrome associated with pazopanib after progression on pembrolizumab

Area of Science:

• Oncology
• Pharmacology
• Immunotherapy

Background:

• Pazopanib is a standard first-line treatment for metastatic renal cell carcinoma (mRCC).
• Programmed cell death protein 1 (PD-1) inhibitors are increasingly used in cancer treatment.
• Combinations of pazopanib and PD-1 inhibitors have shown increased hepatotoxicity in recent trials.

Observation:

• A patient with mRCC developed fatal hepatotoxicity.
• The patient had received prior treatment with a PD-1 inhibitor (pembrolizumab).
• Hepatotoxicity manifested as vanishing bile duct syndrome (VBDS) during pazopanib treatment.

Findings:

• This is the first reported case of pazopanib-induced VBDS.
• The patient's prior exposure to pembrolizumab may have predisposed them to VBDS.
• Pazopanib-induced VBDS occurred in the context of sequential immunotherapy and targeted therapy.

Implications:

• Sequential administration of PD-1 inhibitors followed by pazopanib in mRCC patients may carry significant risks.
• The prolonged half-lives of PD-1 inhibitors could contribute to increased toxicity when combined with pazopanib.
• Further investigation is needed to understand the mechanisms and manage the risks of combined or sequential therapies in mRCC.