Ramucirumab administered at a dose of 10 mg/kg every 21 days for 3 cycles did not produce a statistically or clinically significant prolongation of corrected QT (QTc) interval in patients with advanced cancer, a study published in the journal The Oncologist has shown.1
“Cardiotoxicity can be a serious complication of anticancer therapies,” the researchers wrote. “To enable earlier identification of drug-related cardiac effects, the International Conference on Harmonization (ICH) adopted the ICH E14 Guidelines for evaluating the potential for QT/QTc interval prolongation and proarrhythmic potential for nonantiarrhythmic drugs.”
Ramucirumab is a human immunoglobulin G1 monoclonal antibody that specifically blocks vascular endothelial growth factor receptor-2 (VEGFR-2). It is indicated for the treatment of advanced gastric or gastro-esophageal junction adenocarcinoma, metastatic non-small cell lung cancer, and metastatic colorectal cancer.
For this study, researchers sought to determine if treatment with ramucirumab causes QTc prolongation in patients with advanced cancer. Researchers enrolled 66 patients to receive ramucirumab 10 mg/kg intravenously every 21 days for 3 cycles. Fourteen patients served as positive controls by receiving moxifloxacin 400 mg orally, an antibiotic associated with mild QT prolongation.
Results showed that the average change in QTc interval from baseline was less than 10 milliseconds.
“The results of the evaluation of ramucirumab on the QT/QTc interval show a lack of effect on QTc prolongation in patients with advanced cancer,” the researchers concluded.
1. Olszanski AJ, Smith DC, Camacho LH, et al. Electrocardiographic characterization of ramucirumab on the corrected QT interval in a phase II study of patients with advanced solid tumors [published online ahead of print March 16, 2016]. Oncologist. doi:10.1634/theoncologist.2015-0467.