Bilateral Subfoveal Neurosensory Retinal Detachment Associated With MEK Inhibitor Use for Metastatic Cancer
Three patients who received oral MEK inhibitors developed bilateral subfoveal neurosensory retinal detachment. Patient 1 had metastatic uveal melanoma; the findings resolved without intervention, and subsequent mild uveitis was responsive to topical corticosteroids. Patient 2 had metastatic cholangiocarcinoma, and his findings resolved after 2 weeks of observation. Patient 3 had metastatic rectal cancer, with bilateral uveitis and bilateral subfoveal retinal detachment. Her findings resolved with observation and topical corticosteroids for uveitis. No patient developed permanent ocular sequelae, and none withdrew from the clinical trial of MEK inhibitor therapy.
JAMA Ophthalmol. 2014;132(8):1005 doi:10.1001/jamaophthalmol.2014.976
A MEK inhibitor is a chemical or drug that inhibits the mitogen-activated protein kinase kinase enzymes MEK1 and/or MEK2. They can be used to affect the MAPK/ERK pathway which is often overactive in some cancers. (See MAPK/ERK pathway#Clinical significance.)
Hence MEK inhibitors have potential for treatment of some cancers, especially BRAF-mutated melanoma, and KRAS/BRAF mutated colorectal cancer.
Some MEK inhibitors:
Trametinib (GSK1120212), FDA-approved to treat BRAF-mutated melanoma. Also studied in combination with BRAF inhibitor dabrafenib to treat BRAF-mutated melanoma.
Selumetinib, had a phase 2 clinical trial for non-small cell lung cancer (NSCLC) which demonstrated an improvement in PFS, and is now in phase III development in KRAS mutation positive NSCLC (SELECT-1,NCT01933932). Other clinical trials underway include uveal melanoma, and differentiated thyroid carcinoma.