Purpose: The purpose of this study was to characterize the incidence of cardiovascular events and time to first cardiovascular event due to tyrosine kinase inhibitors (TKIs) in patients with advanced RCC at VASDHS. Additional aims were to describe the current clinical practice management of cardiac monitoring via EKG or ECHO in this patient population.
Background: Over the past 12 years, the US Food and Drug Administration has approved six multitargeted TKIs for the treatment of RCC: axitinib, cabozantinib, lenvatinib, pazopanib, sorafenib and sunitinib. Other than hypertension, most studies of these therapies did not report the incidence of cardiovascular events that occurred during early clinical trials.
Methodology: This was a retrospective study that evaluated the incidence of cardiovascular events in patients diagnosed with advanced RCC who received oral TKI therapy for at least 30 days. The incidence of cardiovascular events was collected in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) grading at predetermined time points from the start of each TKI therapy. Cardiovascular events were defined as hypertension, QT prolongation, congestive heart failure (CHF), stroke, myocardial infarction (MI) and pulmonary hypertension.
Results: Fifty-four patients were included in this study with a median age of 66 years. There were no cardiac events in patients without a history of cardiovascular disease. Eleven patients with a history of cardiovascular disease experienced an adverse cardiac event while taking pazopanib, sorafenib, or sunitinib. The most common adverse events were hypertension (n=6) and MI (n=2). The remaining three patients experienced a stroke, QT prolongation, or CHF. Seventy-three percent of events occurred within four months of starting therapy. Baseline EKG or ECHO were not available for most patients started on TKI therapy and obtained only when patients were symptomatic.
Conclusions: The results of this study indicate a need for baseline and routine monitoring in patients started on oral TKIs with a history of cardiovascular disease to align with the current recommendations as listed in the medication package inserts. Based on the results of this study, baseline and routine monitoring should be considered during the first four months of therapy in patients with a history of cardiovascular disease.
