The Impact of Dose and Simultaneous Use of Acid-Reducing Agents on the Effectiveness of Vemurafenib in Metastatic BRAF V600 Mutated Melanoma: a Retrospective Cohort Study

Lotte M. Knapen*, Rutger H. T. Koornstra, Johanna H. M. Driessen, Bas van Vlijmen, Sander Croes, Stein Schalkwijk, Angela Colbers, Winald R. Gerritsen, David M. Burger, Frank de Vries, Nielka P. van Erp

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Web of Science)

Abstract

The impact of dose and simultaneous use of acid-reducing agents (ARAs) on the effectiveness of vemurafenib is unknown.

To determine the association between progression of metastatic BRAF V600 mutated melanoma and (1) dose reductions of vemurafenib and (2) simultaneous use of vemurafenib and ARAs.

A retrospective cohort study of 112 first-line vemurafenib users for melanoma was conducted (March 2012-March 2016), using electronic patient records and pharmacy dispensing records of a Dutch academic hospital. Cox regression analysis was used to estimate the risk of progression with full-dose (n = 64) versus reduced-dose vemurafenib (n = 48) and with simultaneous use of vemurafenib and ARAs (n = 35) versus vemurafenib alone (n = 77). Analyses were adjusted for age and sex.

In total, disease progression occurred in 55% of treated patients on vemurafenib, with a median progression-free survival of 6.0 (95% confidence interval [CI] 5.0-6.9) months. Compared to patients on vemurafenib alone, there was no increased risk of progression among patients requiring vemurafenib at a reduced dose or among patients receiving simultaneous therapy with vemurafenib and ARAs. In addition, there was no increased risk of progression among patients who used reduced-dose vemurafenib and ARAs versus those receiving full-dose vemurafenib as sole therapy. However, a tendency for progression was observed among patients who used full-dose vemurafenib and ARAs versus full-dose vemurafenib alone (adjusted hazard ratio [HRa] 2.37; 95% CI 0.97-5.76), which became statistically significant in a sensitivity analysis (HRa 4.56; 95% CI 1.51-13.75).

There was no association between the use of vemurafenib in a reduced dose or the simultaneous use of vemurafenib and ARAs and the risk of progression. In addition, there was no association between the simultaneous use of vemurafenib in a reduced dose and ARAs and the risk of progression. However, patients tolerating full-dose vemurafenib simultaneously with ARAs might have an increased risk of progression. This finding requires prospective validation.

Original languageEnglish
Pages (from-to)363-370
Number of pages8
JournalTargeted Oncology
Volume13
Issue number3
DOIs
Publication statusPublished - Jun 2018

Keywords

  • TUMOR RESPONSE
  • OPEN-LABEL
  • PHARMACOKINETICS
  • TOLERANCE
  • SURVIVAL
  • EFFICACY
  • SAFETY

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