Effects of pharmacogenetic variants on vemurafenib-related toxicities in patients with melanoma

Andrew Goey*, Mirjam de With, Bram Agema, Esther Oomen - de Hoop, RK Singh, Astrid van der Veldt, Ron Mathijssen, Ron van Schaik, Sander Bins*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

Aim: The pharmacokinetics and pharmacodynamics of vemurafenib are characterized by a wide interpatient variability. Since multiple polymorphic enzymes and drug transporters are involved in vemurafenib pharmacokinetics, we studied associations of polymorphisms on vemurafenib-associated toxicities. Patients & methods: Prospectively collected samples of 97 melanoma patients treated with vemurafenib alone (n = 62) or in combination with cobimetinib (n = 35) were genotyped for ABCB1 (3435C>T), ABCG2 (421C>A, 34G>A) and CYP3A4 (∗22, 15389C>T) polymorphisms. Associations between these variants and the incidence of toxicities were studied. Results: CYP3A4∗22 was significantly associated with increased risk for grade ≥3 nausea, grade 1-4 hyperbilirubinemia, and cutaneous squamous cell carcinoma. ABCB1 3435C>T was a predictor for grade ≥3 toxicity. Conclusion: Genetic variants in CYP3A4 and ABCB1 are associated with vemurafenib-associated toxicities.

Original languageEnglish
Pages (from-to)1283-1290
Number of pages8
JournalPharmacogenomics
Volume20
Issue number18
DOIs
Publication statusPublished - 2019

Bibliographical note

Publisher Copyright:
© 2019 Future Medicine Ltd.

Research programs

  • EMC MM-03-86-08
  • EMC NIHES-03-30-02

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