Clinical features of serous retinopathy observed with cobimetinib in patients with BRAF‑mutated melanoma treated in the randomized coBRIM study

Abstract

Background: Serous chorioretinopathy has been associated with MEK inhibitors, including cobimetinib. We describe the clinical features of serous retinopathy observed with cobimetinib in patients with BRAFV600-mutated melanoma treated in the Phase III coBRIM study. Methods: In the coBRIM study, 493 patients were treated in two randomly assigned treatment groups: cobimetinib and vemurafenib (n = 247) or vemurafenib (n = 246). All patients underwent prospective ophthalmic examinations at screening, at regular intervals during the study, and whenever ocular symptoms developed. Patients with serous retinopathy were identifed in the study database using a group of relevant and synonymous adverse event terms. Results: Eighty-six serous retinopathy events were reported in 70 patients (79 events in 63 cobimetinib and vemu‑ rafenib-treated patients vs seven events in seven vemurafenib-treated patients). Most patients with serous retinopa‑ thy identifed by ophthalmic examination had no symptoms or had mild symptoms, among them reduced visual acuity, blurred vision, dyschromatopsia, and photophobia. Serous retinopathy usually occurred early during cobi‑ metinib and vemurafenib treatment; median time to onset was 1.0 month. Most events were managed by observa‑ tion and continuation of cobimetinib without dose modifcation and resolved or were resolving by the data cutof date (19 Sept 2014). Conclusions: Cobimetinib treatment was associated with serous retinopathy in patients with BRAFV600-mutated melanoma. Retinopathy was generally asymptomatic or mild. Periodic ophthalmologic evaluations at regular intervals and at the manifestation of any visual disturbance are recommended to facilitate early detection and resolution of serous retinopathy while patients are taking cobimetinib.