(236) Risk factors associated with the incidence of Tyrosine kinase inhibitors-induced cardiac toxicity in cancer patients: a population-based case-control study

Publication Number: 1227

Background: Tyrosine kinase inhibitors (TKIs) are targeted anticancer drugs which are widely used in cancer treatment. Several previous clinical studies have reported that TKIs use has a burden of cardiac toxicity in cancer patients.

Objectives: This study aimed to investigate the association and risk factors between Tyrosine kinase inhibitors use and the risk of cardiac toxicity in cancer patients using population-based data.

Methods: This population-based case-control study analyzed the cardiac toxicity risk in cancer patients treated with TKIs using the Korea National Health Insurance Service-National Sample data from 2002-2019. Cancer and cardiac toxicity were defined using the ICD-10 code. The case was defined as patients diagnosed with cardiac toxicity after a cancer diagnosis. For cases, the index date was defined as the date on which cardiac toxicity was first diagnosed. Controls were randomly matched to the case at a ratio of 1:1 by age-, sex-, and index year. The following risk factors were included in the analysis: the use of any TKI, comorbidities, combination medications, and laboratory data. The chi-square test and conditional logistic regression were used to risk factors estimate the odds ratios (ORs) and adjusted ORs (AOR).

Results: This study included 24,502 cases and 24,502 matched (1:1) controls. TKIs included analysis were Bcr-Abl, VEGF, JAK, and ALK TKIs. The overall use of TKIs was associated with an increased risk of cardiac toxicity in cancer patients. [AORs 2.10, 95% Confidence Interval (Cl) 1.66-2.67]. Comorbidities associated with an increased risk of cardiac toxicity were hypertension (AOR 1.27, 95% CI 1.20-1.34), diabetes mellitus (DM) (AOR 1.23, 95% CI 1.46-1.30), chronic obstructive pulmonary disease (COPD) (AOR 1.13, 95% CI 1.08-1.20), and liver disease (AOR 1.25, 95% CI 1.20-1.31). In concomitant medications, the use of anti-hypertensive drugs (AOR 1.41, 95% CI 1.34-1.49), NSAIDs (AOR 1.43, 95% CI 1.36-1.50), Statin (AOR 1.18, 95% Cl 1.11-1.25), and the use of Acetaminophen (AOR 1.25, 95% Cl 1.20-1.31) were risk factors related to increasing the risk of cardiac toxicity. In the subgroup analysis of TKIs, the use of VEGF TKIs and the use of EGFR TKIs were associated with an increased risk of cardiac toxicity in cancer patients (VEGF: AOR 3.60, 95% CI 2.20-5.88, EGFR: AOR 1.47, 95% Cl 1.10-1.95).

Conclusions: This case-control cohort study revealed that the use of TKIs in patients with cancer significantly increases the risk of cardiac toxicity. As a result of subgroup analysis, Bcr-Abl, VEGF, and EGFR TKIs increased the risk of cardiac toxicity in cancer patients. Thus, close monitoring of cardiovascular function is recommended, especially in patients with TKIs, including VEGF or EGFR TKIs, and patients with comorbidities and concomitant medications.