A Global Non-interventional Study Using Enhanced Pharmacovigilance to Evaluate Potential Sight-Threatening Events and Severe Visual Loss Among Patients Exposed to Crizotinib

Background: Vision disorders are common adverse reactions among non-small cell lung cancer (NSCLC) patients. However, many factors predispose NSCLC patients to develop these outcomes. Objectives: To evaluate the frequency of risk factors for and sequelae of potential sight-threatening events (PSTEs) and severe visual loss (SVL) among crizotinib-treated patients. Methods: From March 2016 to March 2021, we collected reports indicative of PSTE/SVL from crizotinib clinical trials, primary data collection studies, post-marketing spontaneous reports, and other solicited data sources among patients exposed to crizotinib. Variables collected included demographics, crizotinib exposure, medical/ocular history, crizotinib treatment, ophthalmic examinations, and PSTE/SVL outcomes. An external adjudication committee determined whether reported cases were likely to be true cases based on predefined criteria. Results: Cumulatively, 50 reported cases indicative of PSTE/SVL were received. Of these, five were adjudicated as likely to be SVL, 14 as likely to be PSTE, and one as a non-case; 30 had insufficient information. The majority (84.0%) were received via spontaneous reports. Risk factors for PSTE/SVL among the adjudicated cases included a history of ocular disease as well as a history of diabetes, hypertension, hyperlipidemia, and transient ischemic attack/stroke. Moreover, 60.0% of the adjudicated SVL and 14.3% of the adjudicated PSTE cases had a history of brain metastases. Conclusions: We observed a history of ocular diseases, pre-existing medical conditions, and the presence of brain metastases in a large proportion of SVL cases; however, less information was recorded for PSTE cases. Overall, no new vision safety signals associated with crizotinib were identified.