Managing cardiotoxicity in metastatic non-small cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitors (TKIs).

Abstract

e21072 Background: Current guidelines for prevention and monitoring cardiac dysfunction in patients with cancer state there is insufficient evidence to support surveillance strategies for TKIs alone. Furthermore, risk stratification for baseline and frequency of monitoring remains unclear for various products. This study evaluates the current practice for screening and monitoring for cardiotoxicity in patients treated for NSCLC with TKIs and the adherence rate to the standards of care. Methods: A single-center retrospective chart review of 113 patients with metastatic NSCLC who received TKIs at a large academic-community cancer center was performed. The current practice for screening and monitoring for cardiotoxicity and the adherence rate to the suggested standards recommended by the prescribing information of each drug were analyzed. Total incidence of cardiotoxicity was also evaluated. Descriptive statistics were calculated for all demographic variables and clinical outcome endpoints. Incidence of cardiotoxic adverse events were reported as percentages. Results: A total of 113 metastatic NSCLC patients were identified with the majority of patients taking osimertinib (67.3%), alectinib (8.0%), or dabrafenib/trametinib (7.1%) at baseline. Total adherence rate for screening and monitoring for cardiotoxicity as recommended by the prescribing information for all agents was 54%. Cardiotoxicity occurred in 46 (40.7%) patients, presenting most frequently as hypertension and bradycardia. Cohort cardiotoxicity events are summarized in the table below. Decreased left ventricular ejection fraction (LVEF) ≥ 10% or to < 50% occurred in 6/76 (7.9%) patients on osimertinib; however, only 12 (15.8%) patients were able to be assessed due to lack of baseline data. Osimertinib was held and/or discontinued in 3 (3.9%) patients and 1 (1.3%) death resulted due to cardiomyopathy. QTc interval prolongation occurred in 2 (33.3%) patients on afatinib, 1 (20%) patient on crizotinib, and 1 (1.3%) patient on osimertinib. Three (3.9%) patients on osimertinib were diagnosed with atrial fibrillation. Conclusions: The results reported in this study show higher rates of decreased LVEF and similar rates of QTc prolongation with osimertinib compared to prior studies. The increased rate of hypertension observed may be associated with the high rate of uncontrolled blood pressure at baseline. Low adherence rates to the recommendations provided by prescribing information may contribute to increased risk of cardiac dysfunction.[Table: see text]