Ocular toxicity in BRAF mutant cutaneous melanoma patients treated with vemurafenib

Am J Ophthalmol. 2014 Oct;158(4):831-837.e2. doi: 10.1016/j.ajo.2014.07.003. Epub 2014 Jul 15.

Abstract

Purpose: To determine the frequency of ocular adverse effects associated with vemurafenib (PLX4032) treatment for metastatic cutaneous melanoma.

Design: Retrospective review of the clinical study reports from the clinical pharmacology, phase 1, phase 2, and phase 3 trials of vemurafenib.

Methods: The vemurafenib clinical trials were a multicenter series involving adult patients with histologically confirmed, BRAF(V600) mutation-positive, unresectable, stage IIIC or IV melanoma. A total of 855 patients were enrolled in the trials: 568 patients were treated with vemurafenib and 287 patients were treated with dacarbazine.

Results: Among the 568 patients treated with vemurafenib, ocular adverse effects developed in 22% (95% confidence interval [CI], 18.5-25.6). The most common ocular diagnosis was uveitis (4.0%; 95% CI, 2.6-6.0), followed by conjunctivitis (2.8%; 95% CI, 1.6-4.5) and dry eyes (2.0%; 95% CI, 1.1-3.7). All were successfully managed while vemurafenib therapy was continued.

Conclusions: Ocular adverse events and symptoms may be seen in more than one-fifth of patients being treated with vemurafenib. However, vemurafenib can be continued while the ocular symptoms are being managed. The pathogenesis of ocular symptoms in this patient population is unclear; additional studies are necessary.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Conjunctivitis / chemically induced
  • Conjunctivitis / diagnosis
  • Conjunctivitis / drug therapy
  • Dacarbazine / therapeutic use
  • Dry Eye Syndromes / chemically induced
  • Dry Eye Syndromes / diagnosis
  • Dry Eye Syndromes / drug therapy
  • Eye Diseases / chemically induced*
  • Eye Diseases / diagnosis
  • Eye Diseases / drug therapy
  • Female
  • Humans
  • Indoles / adverse effects*
  • Male
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Melanoma / pathology
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Protein Kinase Inhibitors / adverse effects*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Retrospective Studies
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology
  • Sulfonamides / adverse effects*
  • Uveitis / chemically induced
  • Uveitis / diagnosis
  • Uveitis / drug therapy
  • Vemurafenib
  • Young Adult

Substances

  • Antineoplastic Agents, Alkylating
  • Indoles
  • Protein Kinase Inhibitors
  • Sulfonamides
  • Vemurafenib
  • Dacarbazine
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf