Abstract PS7-59: Presence of comorbidities and use of concomitant medications associated with QTC prolongation/torsades de pointes in patients with HR+/HER2- advanced breast cancer
Authors: Mahtani Reshma , Lewis Katie , Clayton Emily , Last Matthew , Mitra Debanjali , Kurosky Samantha 
Published: February 2021

BACKGROUND: Corrected QT (QTc) prolongation is a cardiac condition that may increase the risk of ventricular arrhythmias, including Torsades de Pointes (TdP), and cardiac-related death. QTc prolongation is a notable concern in oncology as drug-induced QTc prolongation is a documented side effect of several anticancer therapies. Moreover, patient-specific risk factors for QTc prolongation such as increased age and a history of cardiovascular disease/events can be common among patients with metastatic breast cancer, which puts this population at an increased baseline risk for QTc prolongation. Female sex is a risk factor itself. The objective of this study was to characterize the presence of comorbidities and use of concomitant medications associated with QTc prolongation/TdP among patients receiving first-line (1L) treatment for HR+/HER2- locally advanced or metastatic breast cancer (aBC).METHODS: Oncologists in France, Germany, Israel, Italy, Spain and the United States abstracted clinical characteristics and medication data from the medical records of patients, aged ≥18, who received 1L treatment for HR+/HER2- aBC between 10/2019 and 02/2020. The presence of comorbidities (e.g., congestive heart failure, myocardial infarction, history of atrial arrythmias) and utilization of concomitant medications (excluding anti-cancer therapies) with known, possible, or conditional risk for QTc prolongation/TdP were summarized. The list of comorbidity risk factors was compiled from a targeted literature search and clinician review. The list of concomitant medications was obtained from crediblemeds.org.RESULTS: A total of 1164 patients with aBC were sampled across the six countries. Among them, 99% were female and the mean age was 62 years. The majority of patients had metastatic disease (85%); 15% had locally advanced disease. Among those with metastatic disease, 47% had visceral metastasis and 34% had bone-only metastasis. At 1L initiation, 84% of patients had an ECOG score of 0/1. Comorbidities associated with risk of QTc prolongation/TdP were observed in 8% of patients; the most frequently observed were congestive heart failure (3%) and history of myocardial infarction (2%) (Table 1). The proportion of patients who received at least one medication associated with risk of QTc prolongation/TdP was 39%. Overall, 42% of patients had at least one comorbidity or medication associated with risk of QTc prolongation/TdP.

CONCLUSIONS: Approximately 2 out of 5 patients receiving 1L treatment for HR+/HER2- aBC had a comorbidity or utilized a concomitant medication that could increase risk of QTc prolongation/TdP. As cardiovascular toxicity is a known side effect associated with several anticancer therapies, the high prevalence of coexisting risk factors among patients receiving 1L treatment underscores the importance of assessing patients’ existing risk when selecting treatments for advanced breast cancer.

Table 1. Presence of Comorbidities and Use of Concomitant Medications with known, possible, or conditional risk for QTc prolongation/TdP in Patients Who Received First-Line Therapy for HR+/HER2- Advanced Breast CancerN%Total Patients1164100ComorbiditiesMyocardial infarction202Congestive heart failure323Moderate or severe liver disease3&lt;1History of QT prolongation3&lt;1Bradyarrhythmia3&lt;1History of atrial arrhythmias282History of ventricular arrhythmias1&lt;1Hypo/hyperkalemia81Hypo/Hypercalcemia81Disorders of magnesium metabolism81Disorders of phosphorus metabolism2&lt;1Unstable angina4&lt;1Presence of comorbidity QTc risk factor948Mean (SD) number of conditions per patient1.3 (.4)Received medication considered a risk factor for QTc prolongation45039Presence of QTc risk factor condition or medication49042

Citation Format: Reshma Mahtani, Katie Lewis, Emily Clayton, Matthew Last, Debanjali Mitra, Samantha Kurosky. Presence of comorbidities and use of concomitant medications associated with QTC prolongation/torsades de pointes in patients with HR+/HER2- advanced breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-59.