A new study from JAMA Ophthalmology has found that patients with lung cancer treated with epidermal growth factor receptor inhibitors (EGFRis) may be at higher risk of new-onset keratitis, particularly those treated with the second-generation EGFRi afatinib.
Give me some background first.
While elevated levels of epidermal growth factor receptor (EGFR) are known to be associated with cancers such as breast cancer, colon adenocarcinoma, and non-small cell lung cancer, EGFRis have been used in the treatment of EGFR variation-positive non-small cell lung cancer.
Currently, there are three generations of EGFRis commonly utilized in treatment:
- First-generation gefitinib and erlotinib
- Second-generation afatinib
- Third-generation osimertinib
Any notable associated adverse events?
A few … such adverse events (AEs) reported following EGFRi therapy include ocular toxicity manifesting as :
- Trichomegaly
- Tear film
- Dry eye
- Ocular epithelium defect
- Keratitis
Of importance: these AEs could have major quality of life consequences for patients receiving these therapies.
Now, talk about the study.
This cohort study of 1,388,108 patients with lung cancer analyzed the incidence of keratitis in patients treated with EGFRi therapies.
Who was included in the study?
The study used patient records collected between May 1, 2003 and October 30, 2023 to categorize patients into exposed versus unexposed groups.
The exposed group included patients over the age of 18 who were treated with EGFRis for lung cancer.
Findings?
Investigators found that patients with lung cancer undergoing EGFRi therapy had an elevated risk of new-onset keratitis compared to the non-exposed group.
The study authors noted specifically that keratoconjunctivitis was a “frequent subtype,” which they argued suggests that patients undergoing EGFRi therapy may also be at higher risk for dry eye disease.
Tell me more.
While the study was not concerned with exploring causes of the enhanced risk, the authors suggested that it could be sourced to one or more of several different mechanisms: other known AEs of EGFRis include trichomegaly, which is known to elevate the risk of corneal cell damage.
In addition, EGFRis could result in an impediment to the “proper repair of damaged corneal epithelial cells.”
Limitations?
The study authors noted that the cohort study could not determine cause-and-effect relationships and was further limited by the lack of a record of chief complaints or specific data from ocular exams.
Take home.
Ultimately, the authors concluded, “These results support the need for prompt diagnosis and management of EGFRi-associated ocular issues to prevent serious complications or treatment disruptions.”