Ocular Toxicity of Mitogen-Activated Protein Kinase Inhibitors

Purbrick, Robert; Osunkunle, Olaoluwakitan A.; Talbot, Denis; Downes, Susan M.

doi:10.1001/jamaoncol.2016.4213

Cited by 8 publications

(5 citation statements)

References 6 publications

(13 reference statements)

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“…In the present study, ophthalmologic toxicity was significantly more frequent in patients who experienced LVEF-D. Although the mechanisms causing the toxicity of BRAF and MEKis are different between the eye and cardiomyocytes, 32,[36][37][38][39][40][41][42][43][44] this association was expected as the majority of patients experienced retinal toxicities (central serous retinopathy and retinal pigment epithelial detachments) that related to MEK inhibition that is itself associated with LVEF-D. [45][46][47][48][49][50] We could not determine herein whether ophthalmological toxicity occurs before or after LVEF-D, but the significant association between these toxicities suggests that there should be a close ophthalmological monitoring when LVEF occurs, but also conversely.…”

Section: F I G U R E 3 Kaplan-meier Estimation Of Overall-survival (A)mentioning

confidence: 73%

Left ventricular ejection fraction decrease related to BRAF and/or MEK inhibitors in metastatic melanoma patients: A retrospective analysis

et al. 2020

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BRAF and MEKis have revolutionized the management of BRAF V600 -mutated melanoma patients. Left ventricular ejection fraction decrease (LVEF-D) related to these treatments has not been thoroughly evaluated to date. The main objective of this study was to describe characteristics of LVEF-D in melanoma patients treated with BRAF and/or MEKis. Metastatic melanoma patients treated with BRAF and/ or MEKis between March 1, 2012 and May 18, 2018 were included retrospectively (Lyon Sud University Hospital, Hospices Civils de Lyon). LVEF-D was defined as a reduction in LVEF ≥10% from baseline to a value <55%; normalization was defined as a value ≥55%. Among the 88 patients included, 12 (13.6%) experienced a LVEF-D, including 10 grade 2 and 2 grade 3. The median onset of which was 11 months (IQR [3-21]). No patient previously treated with beta-blockers (n = 12) experienced a LVEF-D. Analysis of laboratory parameters, electrocardiogram, and transthoracic echocardiography during the follow-up did not find any predictive marker of LVEF-D. All patients who benefited from a specific treatment of LVEF-D had a normalization of LVEF at the end of follow-up. LVEF recovery was significantly better for patients treated with angiotensin converting enzyme inhibitors and beta-blockers than those who did not (P = .019). Ophthalmological adverse events were significantly more frequent in patients who experienced a LVEF-D (P = .006) and the latter did not influence overall-survival (P = .117) or progression-free-survival (P = .297). LVEF-D is a common and easily manageable adverse event due to BRAF and MEKis. Its association with ocular toxicity suggests a close ophthalmological monitoring when LVEF-D occurs. K E Y W O R D Sadverse events, BRAF inhibitor, cardiac toxicity, heart failure, left ventricular ejection fraction, left ventricular systolic dysfunction, MEK inhibitor, metastatic melanoma 2612 | BERGER Et al.

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Section: F I G U R E 3 Kaplan-meier Estimation Of Overall-survival (A)mentioning

confidence: 73%

Left ventricular ejection fraction decrease related to BRAF and/or MEK inhibitors in metastatic melanoma patients: A retrospective analysis

et al. 2020

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“…FGFR signaling is known to occur upstream of the mitogen-activated protein kinase (MAPK) or MEK pathways. 6,7 Perturbing the MAPK or MEK pathways with inhibitors such as pimasertib and dabrafenib has been shown to cause bilateral central serous RDs and more rarely bilateral cystoid macular edema. 8,9 It thus follows that perturbing the MAPK pathway upstream through FGFR could have a similar effect.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor Receptor Inhibitor–Associated Multifocal Serous Retinal Detachments: A Case Report

Kim

Xia

Bracha

et al. 2021

Journal of VitreoRetinal Diseases

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Purpose: This report aims to describe a case of bilateral, multifocal neurosensory retinal detachments that developed during erdafitinib therapy for metastatic urothelial carcinoma. Methods: A case report with color fundus imaging and spectral-domain optical coherence tomography imaging is presented. Results: A 50-year-old man with metastatic urothelial carcinoma had an unremarkable baseline ophthalmic examination prior to starting erdafitinib. At 3-month follow up, an examination revealed bilateral, multifocal retinal detachments. Because the patient was asymptomatic and erdafitinib was the only drug to which his tumor had responded, he was kept on the medication with close ophthalmic monitoring. Conclusions: Erdafitinib, a fibroblast growth factor receptor inhibitor, can cause bilateral, multifocal retinal detachments. Continuation of erdafitinib may be considered in patients without significant visual impairment when the overall benefit of the medication appears to outweigh the risks.

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“…MEK inhibitor-associated ocular hypertension was reported in early-phase clinical trial data of binimetinib, but specifics are scant [ 8 , 9 ]. This report presents three cases of elevated IOP in patients taking three distinct MEK inhibitors other than binimetinib, which would suggest that IOP-elevating effects exist across the class of MEK inhibition.…”

Section: Discussionmentioning

confidence: 99%

MEK Inhibitor-Associated Ocular Hypertension

Collet,

Canestraro,

Abou-Alfa

et al. 2023

Ocul Oncol Pathol

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Mitogen-activated protein kinase kinase (MEK) inhibitors are targeted anti-cancer agents that are prescribed to treat a broad range of cancers. Despite their strong efficacy profile, MEK inhibitors have been associated with ocular toxicities, most notably, self-limited serous detachments of the neurosensory retina. In this report, we outline three cases of a rarely documented toxicity, MEK inhibitor-associated ocular hypertension.

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Ocular Toxicity of Mitogen-Activated Protein Kinase Inhibitors

Cited by 8 publications

References 6 publications

Left ventricular ejection fraction decrease related to BRAF and/or MEK inhibitors in metastatic melanoma patients: A retrospective analysis

Left ventricular ejection fraction decrease related to BRAF and/or MEK inhibitors in metastatic melanoma patients: A retrospective analysis

Fibroblast Growth Factor Receptor Inhibitor–Associated Multifocal Serous Retinal Detachments: A Case Report

MEK Inhibitor-Associated Ocular Hypertension

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