Ocular Toxicity in BRAF Mutant Cutaneous Melanoma Patients Treated With Vemurafenib

• Published in: American journal of ophthalmology 2014-10, Vol.158 (4), p.831-837.e2
• Main Authors: Choe, Christina H, McArthur, Grant A, Caro, Ivor, Kempen, John H, Amaravadi, Ravi K
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibiotics; Antineoplastic Agents, Alkylating - therapeutic use; Clinical trials; Confidence intervals; Conjunctivitis - chemically induced; Conjunctivitis - diagnosis; Conjunctivitis - drug therapy; Dacarbazine - therapeutic use; Demographics; 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; Health Insurance Portability & Accountability Act 1996-US; Humans; Indoles - adverse effects; Kinases; Male; Medical prognosis; Melanoma; Melanoma - drug therapy; Melanoma - genetics; Melanoma - pathology; Metastasis; Middle Aged; Mutation; Neoplasm Staging; Ophthalmology; Protein Kinase Inhibitors - adverse effects; Proto-Oncogene Proteins B-raf - genetics; Retrospective Studies; Review boards; Skin Neoplasms - drug therapy; Skin Neoplasms - genetics; Skin Neoplasms - pathology; Studies; Sulfonamides - adverse effects; Toxicity; Uveitis - chemically induced; Uveitis - diagnosis; Uveitis - drug therapy; Young Adult
• ISSN: 0002-9394; 1879-1891
• DOI: 10.1016/j.ajo.2014.07.003

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, BRAFV600 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.