(264) A Non-Interventional Study Using Multiple Data Sources to Evaluate Potential Sight Threatening Events and Severe Visual Loss Among Patients Exposed to Crizotinib

Publication Number: 595

Background: Crizotinib (XALKORI®) is a selective small-molecule inhibitor of anaplastic lymphoma kinase and ROS1 and its oncogenic variants and received marketing approval in many countries since 2011 for metastatic non-small cell lung cancer.

Objectives: To evaluate the frequency of risk factors for and outcomes of potential sight threatening event (PSTE) and severe visual loss (SVL) among patients exposed to crizotinib.

Methods: From March 31, 2016 to March 31, 2021, this non-interventional (NI), global study collected data on Adverse Event (AE) or Serious Adverse Event (SAE) reports indicative of PSTE or SVL received from crizotinib clinical trials, NI primary data collection studies, post marketing spontaneous reports and other solicited data sources from patients exposed to crizotinib. Variables collected in this study included demographics, crizotinib treatment, medical and ocular history, ophthalmic examinations, and outcomes of any PSTE and SVL cases. An external expert adjudication committee determined whether reported cases were likely to be true cases of PSTE or SVL.

Results: Cumulatively, 50 reported cases indicative of SVL or PSTE were received during the study; 42 of these 50 (84.0%) cases were from the spontaneous reporting system. Of those 50 reported cases, 46 were AE/SAE reports potentially indicative of SVL and 4 were AE/SAE reports potentially indicative of PSTE. Of the 46 reported cases potentially indicative of SVL, 5 cases were adjudicated as likely to be SVL, 10 cases as likely to be PSTE, 1 case to be a non-case, and 30 cases as insufficient information. Adjudication of the 4 reported cases indicative of PSTE found all 4 cases as likely to be PSTE. In total, there were 5 adjudicated SVL cases and 14 adjudicated PSTE cases. Two of the 5 adjudicated SVL cases were reported as unrelated to crizotinib and 3 cases were reported as unknown relationship. One of 14 adjudicated PSTE case was considered related to crizotinib. Associated risk factors for SVL/PSTE among the cases included a prior history of ocular disease (eg., cataracts, macular edema). Medical history among the cases included diabetes, hypertension, hyperlipidemia, and transient ischemic attack/stroke were observed. In addition, 3 of the 5 adjudicated SVL and 2 of the 14 adjudicated PSTE cases had prior history of brain metastases. For outcomes, 4 adjudicated SVL cases were ongoing at the time of the data cutoff date and the status of 1 adjudicated SVL case was unknown. Of the 14 adjudicated PSTE cases, 7 were ongoing, 3 resolved without sequelae, and 4 had an unknown outcome.

Conclusions: Based on the overall assessment of the low number of cases, many of which had limited information, no new ophthalmologic safety signals were identified, and drug causality was not established in these adjudicated cases.