Ocular toxicities associated with targeted anticancer agents: an analysis of clinical data with management suggestions

Abstract

Ocular toxicities are among the most common adverse events resulting from targeted anticancer agents and are becoming increasingly relevant in the management of patients on these agents. The purpose of this study is to provide a framework for management of these challenging toxicities based on objective data from FDA labels and from analysis of the literature. All oncologic drugs approved by the FDA up to March 14, 2015, were screened for inclusion. A total of 16 drugs (12 small-molecule drugs and 4 monoclonal antibodies) were analyzed for ocular toxicity profiles based on evidence of ocular toxicity. Trials cited by FDA labels were retrieved, and a combination search in Medline, Google Scholar, the Cochrane database, and the NIH Clinical Trials Database was conducted. The majority of ocular toxicities reported were low severity, and the most common were conjunctivitis and “visual disturbances.” However, severe events including incidents of blindness, retinal vascular occlusion, and corneal ulceration occurred. The frequency and severity at which ocular toxicities occur merits a more multidisciplinary approach to managing patients with agents that are known to cause ocular issues. We suggest a standardized methodology for referral and surveillance of patients who are potentially at risk of severe ocular toxicity.

Inhibitory Effect of Idelalisib, a Selective Phosphatidylinositol 3-Kinase δ Inhibitor, on Adipogenesis in an In Vitro Model of Graves' Orbitopathy

“…26,27 Idelalisib, a specific PI3K d inhibitor, is globally approved for the treatment of B-cell-related hematologic malignancies; it currently is used in clinical settings and is well-positioned for expanded applications, despite evidence for systemic toxicity, including diarrhea and pneumonitis, and minor ocular adverse events, including nonspecific redness and discharge. 14,28,29 Proinflammatory cytokines, such as IL-6 and IL-8, are strongly associated with development of GO. 30,31 The orbital fibroblasts are the major sources of inflammatory cytokines and have an important role in the development of GO.…”

Evaluation of Prophylactic Corticosteroid Eye Drop Use in the Management of Corneal Abnormalities Induced by the Antibody–Drug Conjugate Mirvetuximab Soravtansine

“…This broad spectrum of ocular toxicities reflects the unique anatomic, physiologic, and biochemical features of the eye (1) and varies with the class of cytotoxic drug used (e.g., alkylating agents, antimetabolites, taxanes, or platinum agents). Ocular side effects have also emerged as an important clinical concern for molecularly targeted therapies entering standard oncology practice, despite these being more tumor selective than traditional cytotoxic chemotherapy (3,4). In some cases they can be attributed to on-target effects due to target antigen expression in the eye, as exemplified by the class effect visual disturbances seen during the early development of MEK and HSP90 inhibitors (5).…”

Diagnosis and Management of Rare Immune-Related Adverse Events

“…The decision to discontinue ICPi therapy is complex and should be made after a thorough discussion among the oncologist, the ophthalmologist, and the patient. Mild to moderate toxicity can be managed medically, whereas severe side effects may require surgical intervention and/or cessation of therapy .…”