Incidence and outcomes of FGFR inhibitor-associated retinopathy of patients treated with oral erdafitinib across the clinical trial program

Abstract Background Fibroblast growth factor receptors inhibitors (FGFRi) are approved treatments for various malignancies. FGFRi-associated retinopathy is a class effect of FGFRi, including erdafitinib, pemigatinib, infigratinib, and rogaratinib. Patients and Methods We summarized FGFRi-associated retinopathy with erdafitinib across five clinical studies in patients with metastatic urothelial cancer (mUC pooled studies) and one study in patients with advanced solid tumors (RAGNAR). We also present changes in visual acuity, retinal pigment epithelial elevation, and subretinal fluid in RAGNAR. Results One hundred and three (21.5%) of 479 patients in the mUC pooled studies and 43/314 (13.7%) patients in RAGNAR experienced FGFRi-associated retinopathy. Most FGFRi-associated retinopathy were Grade 1/2 events. Grade 3 FGFRi-associated retinopathy were infrequent (11/479; 2.3% and 3/314; 1.0%). No Grade 4 events occurred. Most FGFRi-associated retinopathy events (mUC pooled studies, 81/103; 78.6%; RAGNAR, 30/43; 70.0%) occurred within 90 days of treatment initiation and were managed with erdafitinib dose interruption (mUC pooled studies, 41/479 [8.6%]; RAGNAR, 23/314 [7.3%]) or reduction (mUC pooled studies, 58/479 [12.1%]; RAGNAR: 21/314 [6.7%]); few required treatment discontinuation (mUC pooled studies, 14/479 [2.9%]; RAGNAR, 3/314 [1.0%]). By the data cutoff, 63.1% (65/103) patients in the mUC pooled studies and 65.1% (28/43) patients in RAGNAR had their FGFRi-associated retinopathy events resolve. Most unresolved FGFRi-associated retinopathy events were persistent Grade 1 events. In RAGNAR, 92.0% of patients had their visual acuity return to baseline and 78.5% of patients had their retinal pigment epithelial elevation resolve. Conclusions FGFRi-associated retinopathy can be managed with dose reductions, interruptions, or discontinuations. Proactive collaboration between ophthalmologists and oncologists is required to ensure that erdafitinib delivers clinical benefit to patients while managing their potential adverse symptoms of FGFRi-associated retinopathy.