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Catherine Meyerle, Ramaprasad Srinivasan, W. Marston Linehan, Steven Yeh, Emily Chew, Chi-Chao Chan, Farzin Forooghian, Frederick Ferris, Wadih Zein; Visual Function Effects of Foretinib, a Dual MET/VEGFR2 Inhibitor, in a Phase 2 Study for Treatment of Papillary Renal Cell Carcinoma. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5115.
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© ARVO (1962-2015); The Authors (2016-present)
Foretinib, an investigational Met and VEGFR2 tyrosine kinase receptors inhibitor for the treatment of papillary renal cell carcinoma, induced visual complaints in some patients. Exploratory studies to characterize these changes were conducted.
The visual function of 14 NIH papillary renal cell carcinoma patients in a multicenter phase II trial of foretinib (NCT00726323) was evaluated during treatment (12/14 had baseline assessment). Ophthalmic testing for all patients included serial visual acuity (VA), visual field (VF), dark adaptometry (DA), fundoscopy, optical coherence tomography (OCT), fundus autofluorescence photography (FAF), and electroretinography (ERG). Patients with visual symptoms or psychophysical testing change underwent additional ERG and DA. Serum antiretinal antibodies and vitamin A levels were measured.
Six of the 14 patients had ERG and DA abnormalities while on foretinib (4/6 with baseline ERG and DA). The median onset in the 4 patients with baseline testing was 10.8 months (range 5.8-15.2 months). One patient was asymptomatic but developed delayed cone-rod break and elevated DA final thresholds. Three reported slight dark adaptation difficulties confirmed with abnormal DA results and mild scotopic ERG changes. One of these patients improved on DA and ERG two months after stopping foretinib. Two patients who reported dark adaptation trouble had significantly elevated DA thresholds, progressive VF constriction and worsening peripheral FAF changes. These patients also had significantly reduced and delayed ERG responses (scotopic responses most affected). Baseline VA of all patients (range 20/16 -20/32) remained stable throughout follow-up. Serum vitamin A levels were normal in all patients. One mildly symptomatic patient, of the 4 tested amongst the 6 with abnormal ERG and DA, had positive serum anti-retinal antibodies. The rate of 33% (4/12) at the NIH with changes from documented baseline was higher than the 10.8% (8/74) overall rate in the multicenter study that did not include serial ERG and DA at all sites.
Foretinib is associated with possible retinal side effects. The vision care community should be aware of these findings. Additional studies are warranted to evaluate this possible drug toxicity in papillary renal cell carcinoma patients receiving foretinib.
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