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Occurrence of hepatotoxicity with pazopanib and other anti-VEGF treatments for renal cell carcinoma: an observational

Sumitra Shantakumar1, Beth L Nordstrom2, Luc Djousse3

  • 1Worldwide Epidemiology, R&D, GlaxoSmithKline, 150 Beach Road, #26-00 Gateway West, Singapore, 189720, Singapore. sumitra.y.shantakumar@gsk.com.

Cancer Chemotherapy and Pharmacology
|July 21, 2016
PubMed
Abstract

Insights

Pazopanib and other anti-VEGF therapies showed infrequent severe liver injury in renal cell carcinoma patients. This population-based study confirms good hepatic safety for these cancer treatments.

Area of Science:

  • Oncology
  • Pharmacology
  • Hepatology

Background:

  • Renal cell carcinoma (RCC) is a significant health concern.
  • Anti-vascular endothelial growth factor (VEGF) therapies are crucial in RCC treatment.
  • Hepatic safety of these therapies requires careful evaluation in real-world settings.

Purpose of the Study:

  • To assess the hepatic safety of pazopanib compared to other anti-VEGF agents in RCC patients.
  • To quantify the incidence of liver chemistry abnormalities and drug-induced liver injury (DILI).
  • To evaluate safety in a large, population-based cohort.

Main Methods:

  • A population-based cohort study utilized two US healthcare databases (VA, Altos) and the PHARMO network.
  • Liver chemistry data were collected for up to 4 years post-initiation of anti-VEGF therapy.
  • Suspected DILI cases in the VA population underwent chart review and hepatologist adjudication.

Main Results:

  • Pazopanib, bevacizumab, sorafenib, and sunitinib were analyzed in over 1000 RCC patients across databases.
  • Elevated alanine aminotransferase (ALT) levels (≥8x ULN) were infrequent across all cohorts.
  • No Hy's law cases were observed with pazopanib or bevacizumab; one case with sorafenib and two with sunitinib.
  • One adjudicated DILI case occurred with sunitinib; none with pazopanib, bevacizumab, or sorafenib.

Conclusions:

  • Severe liver injury is infrequent with pazopanib and other anti-VEGF therapies in clinical practice for RCC.
  • These findings support the generally favorable hepatic safety profile of these vital cancer treatments.
  • Population-based data provide valuable real-world evidence on anti-VEGF therapy safety.
Keywords:
Anti-VEGFHepatotoxicityLiver chemistryPazopanibRenal cell carcinoma

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