Prevalence Of Ocular Surface Complications Related With A Third-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Epithelial growth factor receptor (EGFR) inhibitors are chemotherapy agents that could make corneal and conjunctival epithelial changes. This study sought to describe the ocular complications after using a recently developed third-generation irreversible EGFR tyrosine kinase inhibitor, Lazertinib (YH-25448, 20 to 320 mg oral, once daily; Genosco Inc., Cambridge, MA, USA).

This is a single-center, retrospective cohort study using medical chart review performed at Yonsei University College of Medicine.

Methods: 437 patients who received Lazertinib therapy for EGFR-mutated non-small cell lung cancer between January 2019 and February 2023 at Yonsei University College of Medicine were retrospectively enrolled. Patients were censored at the end of the study, at the cessation of Lazertinib treatment, at the initiation of a different EGFR or fibroblast growth factor receptor inhibitor, or at death. Ocular complications were categorized into disease-unrelated, disease-related, and treatment-related groups according to their clinical diagnosis. Treatment related complications were identified only if they were not present in the baseline ocular evaluations before initiation of Lazertinib.

During a mean follow-up period of 435.5 ± 292.7 days, 92 patients (21.1%) were referred to the ophthalmology clinic. Disease-related group (n=9) included visual field defect or diplopia due to brain metastasis (n=4) and choroidal metastasis (n=5). Treatment-related group (n=13) included 8 patients (1.8%) with vortex keratopathy, 2 patients (0.5%) with tarsoconjunctival granulation tissue formation with trichomegaly, 2 patients (0.5%) with corneal epithelial defect, and 1 patient (0.2%) with ocular Steven-Johnson syndrome. Overall incidence of treatment-related complications was 3.7 per 100 person-years, and mean increase in logMAR uncorrected visual acuity in the treatment-related group was 0.38 ± 1.08 compared with baseline evaluations.

Newer-generation EGFR agents are known to be associated with a higher incidence of corneal and conjunctival complications compared with previous EGFR inhibitors. In this study, Lazertinib use was associated with risk of ocular surface complications, resulting in a decrease in visual acuity. Therefore, doctors should ensure early recognition and prompt treatment to prevent permanent visual damage.