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Characterization of Serous Retinopathy Associated with Cobimetinib: Integrated Safety Analysis of Four Studies
Giulio Barteselli1, Grant R Goodman1, Yogesh Patel2
1Genentech, Inc. (a Member of the Roche Group), 1 DNA Way, South San Francisco, CA, USA.
Introduction And Objective:
Serous retinopathy can be associated with MEK inhibitors, including cobimetinib. We present results of an integrated safety analysis to further characterize ocular functional and structural changes due to serous retinopathy.
Methods:
Four studies evaluating cobimetinib at the approved dose and schedule in combination with other oncology drugs were included. Study CO39721 incorporated standardized ophthalmologic assessments to fully characterize serous retinopathy events over time and was the primary study for analysis. Supporting information was provided by studies GO28141, WO29479, and GO30182.
Results:
In total, 655 patients received one or more doses of cobimetinib and comprised the safety-evaluable population. Overall, 117 patients (17.9%) had one or more serous retinopathy events, 24 (3.7%) had two or more events, and four (0.6%) had three or more events. Grade 3 events occurred in < 2.5% of patients. In CO39721, the median time to onset was 15 days (range 7-111); median time to resolution of first occurrence was 26 days (range 6-591 + days). Twelve of 25 patients (48.0%) recovered without a dose modification and 4/25 (16.0%) were recovered/recovering following a dose modification. The most frequent presentation of serous retinopathy was focal subretinal fluid on optical coherence tomography (62.8% of cases); in some instances (25.7% of cases), subretinal fluid was multifocal. There was no loss of visual function or visual acuity at serous retinopathy onset or resolution.
Conclusions:
Results from this integrated safety analysis indicate that cobimetinib-associated serous retinopathy can be managed with or without a dose modification of cobimetinib at the discretion of the treating physician. No visual loss or permanent retinal damage was identified on comprehensive ophthalmologic assessments.
Clinical Trial Registration:
ClinicalTrials.gov identifiers: NCT03178851, NCT01689519, NCT02322814, and NCT02788279.
Insights
Serous retinopathy associated with cobimetinib, a MEK inhibitor, is manageable with or without dose modification, with no identified visual loss or permanent retinal damage.
Area of Science:
- Ophthalmology
- Oncology
- Pharmacology
Background:
- Serous retinopathy is a known ocular side effect of MEK inhibitors like cobimetinib.
- Understanding the functional and structural ocular changes associated with cobimetinib is crucial for patient management.
Purpose of the Study:
- To characterize ocular functional and structural changes in patients treated with cobimetinib.
- To analyze the incidence, timing, and resolution of serous retinopathy events.
Main Methods:
- Integrated safety analysis of four clinical studies involving cobimetinib in combination with other oncology drugs.
- Standardized ophthalmologic assessments were used, with study CO39721 being the primary source for detailed characterization.
Main Results:
- 17.9% of 655 patients experienced serous retinopathy events, with Grade 3 events in <2.5%.
- Median time to onset was 15 days, and median time to resolution was 26 days.
- 48% recovered without dose modification; no visual loss or acuity impairment was observed.
Conclusions:
- Cobimetinib-associated serous retinopathy is manageable, with treatment decisions made at the physician's discretion.
- Comprehensive assessments confirmed no permanent retinal damage or visual loss.
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