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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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Nephrotoxicity of the BRAF Inhibitors Vemurafenib and Dabrafenib

Kenar D Jhaveri1, Vipulbhai Sakhiya1, Steven Fishbane1

  • 1Division of Nephrology, Hofstra North Shore LIJ School of Medicine, North Shore University Medical Center, Long Island Jewish Medical Center, Great Neck, New York.

JAMA Oncology
|July 17, 2015
PubMed
Abstract

Insights

Vemurafenib and dabrafenib, BRAF inhibitors for melanoma, show potential kidney damage. Vemurafenib appears more nephrotoxic, particularly in men. Monitoring renal function is crucial for patients on these therapies.

Area of Science:

  • Oncology
  • Pharmacology
  • Nephrology

Background:

  • Selective BRAF inhibitors like vemurafenib and dabrafenib improve survival in BRAF V600-mutant metastatic melanoma.
  • These targeted therapies represent a significant advancement in melanoma treatment.

Purpose of the Study:

  • To evaluate and compare the renal toxic effects of vemurafenib and dabrafenib.
  • To identify patient populations at higher risk for drug-induced kidney injury.

Main Methods:

  • Analysis of Food and Drug Administration Adverse Event Reporting System (FAERS) data for vemurafenib and dabrafenib.
  • Review of reported cases of acute kidney injury, hypokalemia, and hyponatremia associated with these BRAF inhibitors.

Main Results:

  • 132 cases of acute kidney injury reported with vemurafenib versus 13 with dabrafenib.
  • Renal injury was significantly more common in male patients for both drugs.
  • Electrolyte abnormalities, including hypokalemia and hyponatremia, were also reported.

Conclusions:

  • Vemurafenib demonstrates a higher incidence of nephrotoxicity compared to dabrafenib.
  • Male melanoma patients receiving BRAF inhibitors may be at increased risk for renal adverse events.
  • Monitoring renal function and electrolytes is recommended for patients treated with vemurafenib or dabrafenib.

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