Ocular Toxicity in BRAF Mutant Cutaneous Melanoma Patients Treated With Vemurafenib

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. (C) 2014 by Elsevier Inc. All rights reserved.