Corneal Perforation as a Possible Ocular Adverse Event Caused by Cabozantinib: A Clinical Case and Brief Review

Abstract

Background: Cabozantinib is a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor (VEGFR-TKI). These drugs are employed as therapy for several malignancies. In detail, Cabozantinib has demonstrated its efficacy against several malignancies. On the other hand, Cabozantinib and other VEGFR-TKIs can be responsible for various adverse events (AEs), in particular hepatic and dermatological AEs. Methods: To date, limited data are available in the literature regarding ocular AEs due to therapy with these drugs. In this regard, one case of corneal perforation during treatment with a VEGFR-TKI, Regorafenib, has been reported, while there are no data about Cabozantinib. In this paper, we present another clinical case of corneal perforation in a patient affected by advanced RCC and treated with Cabozantinib as a second-line therapy. The patient started Cabozantinib at the dosage of 60 mg/die although it was necessary to apply some dose reductions because of grade 2 AEs (according to CTCAE v6.0), such as asthenia, diarrhea, dysgeusia, and loss of appetite. Results: After approximately 15 months of treatment, the patient began to experience pain and vision loss in the right eye. A diagnosis of corneal perforation was made, followed by medical and surgical treatment. As regards the etiology of this pathology, all other possible causes were excluded, including a history of ocular disease, contact trauma, exposure to damaging agents (e.g., chemical agents and prolonged use of drugs such as topical NSAIDs), infections, or dry eye. Therefore, we hypothesized a correlation with Cabozantinib's mechanisms of action and paused its administration. Conclusions: Cabozantinib may alter the ocular environment due to a lack of or imbalance in growth factors in the tear film, with a reduction in corneal epithelium proliferation. This condition might cause dry eye and a delay in corneal healing. Therefore, particular importance should be placed on ophthalmologic surveillance during treatment with these drugs in patients who develop ocular symptoms. Further in vitro and in vivo studies are necessary to deepen the knowledge about VEGFR-TKI-mediated ocular AEs.

Keywords: Cabozantinib; corneal perforation; ocular adverse event; renal cell carcinoma; vascular endothelial growth factor receptor.

Figure 1

The red arrow indicates the marginal corneal ulcer with perforation.

Figure 2

(a) Lateral tarsorrhaphy with 6/0 Prolene suture and silicon hose; (b) eye in the primary position with lateral tarsorrhaphy and the cornea covered by triple HAM layers; (c) eye facing left to better visualize the perforated area covered by the eyelid.

Figure 3

(a) The eye in the primary position with lateral tarsorrhaphy covering the site of ulceration; the central cornea cleared after HAM absorption; (b) the eye facing left to better visualize the perforated area (red arrow) covered by the residual HAM and conjunctiva.