MEK inhibitor-associated retinopathy (MEKAR) in metastatic melanoma: Long-term ophthalmic effects
Open accessAbstract
Background Mitogen-activated protein kinase kinase (MEK) inhibitors have aroused considerable interest in oncology. Activity has been demonstrated in various types of cancer, especially melanoma. MEK inhibitors induce a transient retinopathy, considered to be a class effect. At present, only sparse data are available on retinal effects with long-term MEK inhibition.Patients and methods In this prospective, observational study, patients with advanced melanoma participating in different phase 1/2 or phase 3 clinical trials were treated with the MEK inhibitor binimetinib, with a v-Raf murine sarcoma viral oncogene homolog B (BRAF) inhibitor, or with combination therapy. They underwent regular ophthalmological examinations including determination of visual function, biomicroscopy, dilated fundoscopy and optical coherence tomography (OCT) for a period of up to 2 years. Retinopathy was diagnosed on defined OCT criteria.Results Sixty-two patients were investigated between 1st October 2011 and 31st July 2015: 13 were treated with the MEK inhibitor binimetinib alone, 10 with a selective BRAF inhibitor, and 39 with combination therapy. In 92% of patients on monotherapy and 100% of those on combination treatment, binimetinib caused dose-related lesions with serous neuroretinal detachments and oedema, strongly dependent on the time after medication. With continued treatment, retinal volume and thickness decreased to levels below baseline, without any apparent functional deficits or changes in structural integrity.Conclusions Binimetinib induces a specific retinopathy with daily fluctuations depending on the time interval after medication. The retinopathy partially recovers, but can still be detected many months later. Retinal thinning, possible first signs of retinal atrophy have been observed after long-term treatment, but, so far, without functional relevance.
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MEKAR is usually mild, self-limited, and may subside after continuous use of the drug for weeks or months, or discontinuation, thereby restoring the normal visual function of the retina, with some exceptions.
“MEKAR is usually mild, self-limited, and may subside after continuous use of the drug for weeks or months, or discontinuation, thereby restoring the normal visual function of the retina, with some exceptions [ 218 ]”
From MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges (2023) · cites this paper as [218]
Binimetinib induces MEKAR with daily fluctuations depending on the time interval after medication, which only partially recovers, being detectable many months later and sometimes leading to subclinical retinal thinning.
“binimetinib, a MEK inhibitor, induces MEKAR with daily fluctuations depending on the time interval after medication, which only partially recovers, being detectable many months later and sometimes leading to subclinical retinal thinning [ 218 ]”
From MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges (2023) · cites this paper as [218]
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- Authors
- Urner-Bloch, U., Urner, M., Jaberg-Bentele, N., Frauchiger, A. L., Dummer, R., & Goldinger, S. M.
- Affiliations
- University Hospital Zurich (CH)
- University of Zurich (CH)
- Corresponding author
- Dummer, R.
- Venue
- European Journal of Cancer
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 65
- Pages
- 130-138
- ISSN
- 0959-8049 (ISSN-L)
- OpenAlex
- W2509999533
- Cited by
- 82
- References
- 28
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 8 · 2023: 7 · 2022: 10 · 2021: 10 · 2020: 8 · 2019: 11 · 2018: 6 · 2017: 4 · 2016: 1
- FWCI
- 7.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Novartis Pharma Schweiz
- Topics
- Health Sciences › Medicine › Ophthalmology › Drug-Induced Ocular Toxicity
- Health Sciences › Medicine › Ophthalmology › Ocular Oncology and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- binimetinib, metastatic melanoma, BRAF inhibitors, retinal edema, retinal atrophy, combination therapy, visual function
- MeSH terms
- Aged, Antineoplastic Agents, Benzimidazoles, Dose-Response Relationship, Drug, Female, Humans, Male, Melanoma, Middle Aged, Prospective Studies, Retinal Diseases, Skin Neoplasms, Mitogen-Activated Protein Kinase Kinases, Protein Kinase Inhibitors, Proto-Oncogene Proteins B-raf
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