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

Journal of Translational Medicine

Research

Jean-Jacques Grob¹  Jeffrey T. R. Evans²  Lorenza Di Guardo³  Jessie J. Hsu⁴  Susan Eng⁴  Anne Uyei⁴  Giulio Barteselli⁴  Paolo A. Ascierto⁵  Antoni Ribas⁶  Brigitte Dréno⁷  Alfredo Venosa⁸  Grant A. McArthur⁹  James Larkin^1,10  Luis de la Cruz-Merino^1,11  Antonio Gomez-Escobar^1,11 

[1] Aix-Marseille University, Hôpital de la Timone, Marseille, France;Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, UK;Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;Genentech, Inc., South San Francisco, CA, USA;Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy;Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, CA, USA;Nantes University, Nantes, France;Ospedale Monaldi, Naples, Italy;Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia;University of Melbourne, Parkville, VIC, Australia;Royal Marsden NHS Foundation Trust, London, UK;Servicio de Oncología Médica, Hospital Universitario Virgen Macarena, Avenida Doctor Fedriani 3, 41071, Seville, Spain;

关键词: Cobimetinib;    MEK inhibition;    Melanoma;    Serous retinopathy;    Visual disturbance;   

DOI  :  10.1186/s12967-017-1246-0

 received in 2017-03-24, accepted in 2017-06-15,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundSerous 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.MethodsIn 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.ResultsEighty-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).ConclusionsCobimetinib 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.Trial Registration Clinicaltrials.gov (NCT01689519). First received: September 18, 2012

【 授权许可】

CC BY   
© The Author(s) 2017