Association of QT interval-prolonging drugs with clinical trial eligibility in patients with advanced cancer

• Published in: Frontiers in cardiovascular medicine 2022-12, Vol.9, p.894623
• Main Authors: Rowe, Elizabeth J, Shugg, Tyler, Ly, Reynold C, Philips, Santosh, Rosenman, Marc B, Callaghan, John T, Radovich, Milan, Overholser, Brian R, Schneider, Bryan P, Tisdale, James E, Skaar, Todd C
• Format: Article
• Language: English
• Subjects: cancer; Cardiovascular Medicine; clinical trial eligibility; clinical trial exclusion; QT interval; QT-prolonging drugs; QTc
• ISSN: 2297-055X; 2297-055X
• DOI: 10.3389/fcvm.2022.894623

Drug-induced prolongation of the heart rate-corrected QT interval (QTc) is associated with increased risk for the potentially fatal arrhythmia torsades de pointes. Due to arrhythmia risk, clinical trials with cancer therapeutics often exclude patients based on thresholds for QTc prolongation. Our objective was to assess associations between prescriptions for QT-prolonging drugs and the odds of meeting cancer trial exclusionary QTc thresholds in a cohort of adults with advanced cancer. Electronic health records were retrospectively reviewed for 271 patients seen at our institutional molecular solid tumor clinic. Collected data included demographics, QTc measurements, ventricular arrhythmia-related diagnoses, and all inpatient and outpatient prescriptions. Potential associations were assessed between demographic and clinical variables, including prescriptions for QT-prolonging drugs, and QTc measurements. Women had longer median QTc measurements than men ( = 0.030) and were prescribed more QT-prolonging drugs during the study ( = 0.010). In all patients, prescriptions for QT-prolonging drugs were associated with longer median and maximum QTc measurements at multiple assessed time points (i.e., for QT-prolonging drugs prescribed within 10, 30, 60, and 90 days of QTc measurements). Similarly, the number of QT-prolonging drugs prescribed was correlated with longer median and maximum QTc measurements at multiple time points. Common QTc-related exclusionary criteria were collected from a review of ClinicalTrials.gov for recent cancer clinical trials. Based on common exclusion criteria, prescriptions for QT-prolonging drugs increased the odds of trial exclusion. This study demonstrates that prescriptions for QT-prolonging drugs were associated with longer QTc measurements and increased odds of being excluded from cancer clinical trials.