gdc-0973 and Retinal-Diseases

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.. 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.. 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.. 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.. ClinicalTrials.gov identifiers: NCT03178851, NCT01689519, NCT02322814, and NCT02788279.

Topics: Azetidines; Humans; Piperidines; Protein Kinase Inhibitors; Retinal Diseases

Topics: Azetidines; Craniopharyngioma; Female; Fluorescein Angiography; Fundus Oculi; Humans; MAP Kinase Kinase 1; Middle Aged; Piperidines; Pituitary Neoplasms; Protein Kinase Inhibitors; Retinal Diseases; Tomography, Optical Coherence; Vemurafenib

Topics: Aged; Antineoplastic Agents; Azetidines; Breast Neoplasms; Female; Fluorescein Angiography; Humans; MAP Kinase Kinase 1; Neoplasm Staging; Piperidines; Retinal Diseases; Tomography, Optical Coherence; Visual Acuity

Three clinical cases are presented of MEK retinopathy associated with the combination of cobimetinib and vemurafenib characterised by alteration of the retinal pigment epithelium and neurosensory detachment. Two of the cases conserved the vision of the unit, and the third developed a large bilateral neurosensory detachment with final visual acuity of 0.6 for the right eye and 0.1 for the left one.. The new therapeutic strategies against metastatic cutaneous melanoma condition the appearance of alterations of the pigmentary epithelium of the retina with serous detachments, leading to close monitoring with macular optical coherence tomography.

Topics: Antineoplastic Agents; Azetidines; Female; Humans; Male; Melanoma; Middle Aged; Mitogen-Activated Protein Kinases; Piperidines; Retinal Diseases; Vemurafenib