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 BRAF V600-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 identified 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 vemurafenib-treated patients vs seven events in seven vemurafenib-treated patients). Most patients with serous retinopathy identified 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 cobimetinib and vemurafenib treatment; median time to onset was 1.0 month. Most events were managed by observation and continuation of cobimetinib without dose modification and resolved or were resolving by the data cutoff date (19 Sept 2014).

CONCLUSIONS:

Cobimetinib treatment was associated with serous retinopathy in patients with BRAF V600-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. Trial Registration Clinicaltrials.gov (NCT01689519). First received: September 18, 2012.

• Authors: Luis de la Cruz-Merino, Lorenza Di Guardo, Jean-Jacques Grob, Alfredo Venosa, James Larkin, Grant A McArthur, Antoni Ribas, Paolo A Ascierto, Jeffrey T R Evans, Antonio Gomez-Escobar, Giulio Barteselli, Susan Eng, Jessie J Hsu, Anne Uyei, Brigitte Dréno
• Journal: Journal of translational medicine (J Transl Med) Vol. 15 Issue 1 Pg. 146 (06 24 2017) ISSN: 1479-5876 [Electronic] England
• PMID: 28646893 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Azetidines
• Indoles
• Piperidines
• Sulfonamides
• Vemurafenib
• Proto-Oncogene Proteins B-raf
• cobimetinib

Topics

• Adult
• Aged
• Azetidines (adverse effects, therapeutic use)
• Central Serous Chorioretinopathy (chemically induced, diagnostic imaging, pathology)
• Female
• Humans
• Indoles (therapeutic use)
• Male
• Melanoma (drug therapy, pathology)
• Middle Aged
• Mutation (genetics)
• Piperidines (adverse effects, therapeutic use)
• Proto-Oncogene Proteins B-raf (genetics)
• Recurrence
• Skin Neoplasms (drug therapy, pathology)
• Sulfonamides (therapeutic use)
• Time Factors
• Vemurafenib