Electrocardiographic Characterization of Ramucirumab on the Corrected QT Interval in a Phase II Study of Patients With Advanced Solid Tumors

• Type of Material: Article
• Authors: Anthony J. Olszanski, Fox Chase Canc Ctr; David C. Smith, University of Michigan; Luis H. Camacho, Ctr Oncol & Blood Disorders; John Thompson, Seattle Cancer Care Alliance; Suresh S Ramalingam, Emory University; R Donald Harvey, Emory University; Luis Campos, Oncol Consultants; David Ferry, Eli Lilly & Co; Shande Tang, Eli Lilly & Co; Ling Gao, Eli Lilly & Co; Howard Safran, Rhode Island Hospital
• Language: English
• Date: 2016-04-01
• Publisher: AlphaMed Press: Oncologist
• Publication Version: Final Published Version
• Copyright Statement: ©AlphaMed Press; the data published online to support this summary is the property of the authors.
• Final Published Version (URL): http://dx.doi.org/10.1634/theoncologist.2015-0467
• Title of Journal or Parent Work: Oncologist
• ISSN: 1083-7159
• Volume: 21
• Issue: 4
• Start Page: 402
• End Page: 403
• Keywords: DOUBLE-BLIND; PLACEBO; Science & Technology; MULTICENTER; GROWTH-FACTOR RECEPTOR-2; Oncology; TRIAL; Life Sciences & Biomedicine
• Research Categories: Health Sciences, General; Health Sciences, Oncology

Abstract

Background. Ramucirumab is a human immunoglobulin G1 monoclonal antibody that specifically blocks vascular endothelial growth factor receptor-2 and is approved for the treatment of advanced gastric, non-small cell lung, and colorectal cancers. This phase II study was conducted to determine if treatment with ramucirumab causes prolongation of the corrected QT interval usingFridericia’s formula(QTcF) inpatientswithadvancedcancer. Methods. Patients received intravenous ramucirumab (10 mg/kg) every 21days for3 cycles.The first 16 patients received moxifloxacin (400 mg orally), an antibiotic associated with mild QT prolongation as a positive control. During cycle 3, determination of QTcF prolongation was made with triplicate electrocardiograms at multiple time points to compare with baseline. Results. Sixty-six patients received therapy; 51 patients completed 9 or more weeks of therapy for the complete QTcF evaluation period. The upper limit of the 90% two-sided confidence intervals for the least square means of change in QTcF from baseline at each time point was less than 10milliseconds. Concentration-QTcF analysisshowedavisible, but not significant, negative association between ramucirumab concentration and QTcF change from baseline. Conclusion. Ramucirumab at a dose of 10 mg/kg administered every 21 days for 3 cycles did not produce a statistically or clinically significant prolongation of QTcF.