FGFR Inhibitor Cancer Drugs Linked to Dry Eye and Corneal Damage in FAERS Analysis
核心洞察
A FAERS pharmacovigilance analysis identified distinct ocular safety signals for three approved FGFR (搜索) inhibitors (erdafitinib, pemigatinib, futibatinib), with 12.6% of reported adverse events being ocular.
Erdafitinib showed the broadest and strongest signals, led by corneal thinning (ROR 321), ocular toxicity (ROR 225), and xerophthalmia (ROR 138), many of which are absent from its FDA label.
Pemigatinib skewed toward retinal fluid problems, including serous retinal detachment (ROR 180) and subretinal fluid (ROR 165), while futibatinib generated only a dry-eye signal (ROR 36.12).
A retrospective pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) has mapped the ocular safety signals associated with three approved fibroblast growth factor receptor inhibitors (FGFRis), revealing several signals that extend beyond what current drug labeling captures. The findings, published in the American Journal of Ophthalmology, support proactive eye monitoring as these cancer drugs move into wider clinical use.
The three FGFR (搜索) inhibitors examined—erdafitinib, pemigatinib, and futibatinib—treat FGFR-altered cancers such as urothelial carcinoma (搜索) and cholangiocarcinoma (搜索). As their use expands, attention has turned to class-specific toxicity, with ocular adverse events among the most frequently reported, particularly dry eye and a range of corneal and retinal abnormalities. Clinical trials have documented visual disturbances in up to 25% of treated patients, including blurred vision, dry eye, retinal detachment, and keratitis. However, investigators noted that trial populations are small and tightly screened, likely undercounting the real-world spectrum of ocular toxicity.
Study Design and Population
The research team conducted a retrospective pharmacovigilance analysis of FAERS through OpenVigil 2.1, pulling reports in which erdafitinib, pemigatinib, or futibatinib was listed as the primary suspect drug. Reporting odds ratios (RORs) were calculated for each drug–ocular adverse event pair against all other drugs in the database, covering the period from April 19, 2019 to June 30, 2025.
The analysis captured 1,582 unique FGFRi-linked adverse events, of which 200 (12.6%) were ocular. Among the reports, 562 came from male patients, 414 from female patients, and 606 did not specify sex. The mean age was 63.7 years. The United States filed the majority of reports (73.9%), followed by France (8.2%) and Canada (2.5%). Erdafitinib accounted for the bulk of ocular events at 150 (75%), versus 44 (22%) for pemigatinib and 6 (3%) for futibatinib.
Distinct Ocular Safety Profiles
Erdafitinib carried the broadest and strongest signals. The highest were corneal thinning (ROR 321; 95% CI 102 to 1009), ocular toxicity (ROR 225; 95% CI 117 to 439), and xerophthalmia (ROR 138; 95% CI 44 to 432). By raw count, dry eye led (n=31), followed by eye disorder (n=24), retinal detachment (n=15), and visual impairment (n=14).
Pemigatinib skewed toward retinal fluid problems. Its top signals were serous retinal detachment (ROR 180; 95% CI 67 to 484), subretinal fluid (ROR 165; 95% CI 68 to 398), and retinal pigment epithelium detachment (ROR 110; 95% CI 35 to 344). Dry eye was again the most reported event by count (n=20).
Futibatinib generated a single ocular adverse event signal: dry eye (n=6), at an ROR of 36.12 (95% CI 15.76 to 82.74).
Signals Beyond Current Labeling
Many of the erdafitinib signals do not appear on its FDA label, including xerophthalmia, ulcerative keratitis (ROR 46), corneal thinning, chorioretinopathy (ROR 121), and maculopathy. For pemigatinib, events beyond the label included subretinal fluid, serous retinal detachment, retinal detachment, and ocular hyperemia—the latter being the lone event that fell short of statistical significance after Bayesian shrinkage.
On the labels themselves, erdafitinib lists dry eye in 28% of patients, pemigatinib lists dry eye in 31%, and futibatinib lists dry eye in 15%. The FAERS dry-eye reporting aligned with all three agents. Only one mismatch emerged: futibatinib's label flags retinal pigment epithelium detachment in 9% of patients, but the analysis found no such signal for it. The authors attributed this to FAERS capturing mainly symptomatic events, whereas small retinal pigment epithelium detachments often remain asymptomatic and resolve on their own.
Mechanism and Clinical Implications
The authors argued that the signals justify proactive ophthalmic monitoring for patients on FGFR (搜索) inhibitors. On mechanism, they noted that these are pan-FGFR agents, and FGFR1–4 are distributed throughout the retina and concentrate in the retinal pigment epithelium, which may predispose those structures to toxicity. They also pointed to erdafitinib's longer elimination half-life—roughly 59 hours, versus 15.4 hours for pemigatinib and 2.9 hours for futibatinib—as a plausible reason it dominates the corneal signals.
A meibomian gland angle is consistent with prior work: pemigatinib has been shown to drive meibomian gland atrophy and faster tear film breakup, which could explain the dry eye and compensatory tearing observed across all three agents.
For clinicians managing patients on FGFR (搜索) inhibitors, the takeaway is early counseling that dry eye and increased lacrimation are common, and that more serious retinal events can occur but usually resolve once the drug is stopped. Eyecare providers should match erdafitinib for corneal and retinal toxicity and pemigatinib for retinal fluid and serous detachments. Baseline and ongoing eye monitoring is a reasonable default while these drugs see broader clinical use.
Study Limitations
The usual pharmacovigilance caveats apply. RORs are sensitive to small cell counts, so rare events can produce inflated, unstable estimates—a particular concern here, given that several signals rested on three to five reports. FAERS is subject to underreporting, duplicate entries, and missing clinical detail, and it cannot establish incidence, severity, or causality. With polypharmacy common in oncology, isolating the responsible drug is difficult, raising the risk of confounding. Erdafitinib was approved first (2019), giving it a longer surveillance window than pemigatinib (2020) or futibatinib (2022), which partly explains its larger share of reports; a lower report count should not be read as lower toxicity. The authors framed the results as hypothesis-generating rather than confirmatory.