Novel ocular toxicity associated with fibroblast growth factor receptor (FGFR) inhibitors in cancer treatment: observational case series

Aims

To describe novel ocular toxicity in patients with metastatic cancer undergoing chemotherapy with fibroblast growth factor receptor (FGFR) inhibitors.

Methods

This observational case series study included five patients with advanced cancer who received selected pan-FGFR inhibitors as single chemotherapy in the framework of a dose-finding study and phase I and phase II clinical studies. In all cases, subfoveal neurosensory retinal detachment was diagnosed. All patients underwent complete ophthalmic examination with swept source optical coherence tomography (SS-OCT) and OCT angiography in selected cases.

Results

SS-OCT showed subfoveal neuroretinal detachment soon after treatment induction with FGFR inhibitors. Lesions were asymptomatic with a tendency to persist at follow-up without improvement. Complete resolution of subretinal fluid was only observed in two patients after a two-level dose reduction and after 4 weeks of stopping medication, respectively. In the remaining three patients, subfoveal neuroretinal detachment showed small fluctuations at follow-up visits. Permanent sequelae did not develop and none of the patients was withdrawn from clinical studies because of ocular toxicity. No abnormalities in retinal or choroidal vasculature as well as choroidal thickness were documented.

Conclusions

Detailed characteristics of subfoveal neurosensory retinal detachment associated with FGFR inhibitor use for metastatic cancer are reported for the first time. Choroidal vasculature seems uninvolved. Isolated subfoveal lesions and longer persistence of subretinal fluid may be differential features from retinal toxicity associated with mitogen-activated protein kinase inhibitors.

Trial registration number

NCT02150967; NCT 01976741; NCT 02052778, Pre-results.

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