Risk of Heart Failure Hospitalization in Patients Treated With Osimertinib: A Population-Based Retrospective Cohort Study.

Background: Osimertinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, is used to treat patients with epidermal growth factor receptor-mutant non-small-cell lung cancer. Although osimertinib has been linked to heart failure (HF), detailed risk estimates remain unclear.

Objectives: The aim of this study was to examine the association between osimertinib use and HF hospitalization.

Methods: In this retrospective cohort study using a large-scale Japanese claims database, patients diagnosed with lung cancer between April 2008 and December 2021 who received cancer therapy were identified. Patients were categorized into osimertinib and control groups according to treatment received. The incidence of HF hospitalization during the treatment period was compared between the groups. Multivariable analyses were performed before and after propensity score matching.

Results: The osimertinib and control groups included 11,391 and 108,144 patients, respectively. Among the entire cohort, the median age was 70 years (Q1-Q3: 64-76 years), and the median follow-up duration was 173 days (Q1-Q3: 73-448 days). The incidence of HF hospitalization was 9.9 and 4.1 cases per 1,000 person-years in the osimertinib and control groups, respectively. In multivariable analysis, osimertinib was associated with a higher risk for HF hospitalization than control therapy (subdistribution HR: 2.56; 95% CI: 2.07-3.18; P < 0.001). This association remained significant after propensity score matching (subdistribution HR: 2.29; 95% CI: 1.62-3.24; P < 0.001).

Conclusions: Osimertinib use was associated with an increased risk for HF hospitalization. Cardiac function should be closely monitored in patients receiving osimertinib.