Simple Summary
Osimertinib is a widely used and highly effective oral therapy for lung cancer driven by specific genetic alterations. Although it is generally well tolerated, some patients are hospitalized for heart failure during treatment, and doctors currently have no simple means of identifying those at risk in advance. Using a large real-world health database, we found that older age, previous hospitalization for heart failure, an irregular heartbeat, and the use of certain heart medications before treatment were associated with these hospitalizations. We combined these factors into a simple scoring chart. This chart cannot replace cardiac ultrasound scans or blood tests, and our data cannot establish that osimertinib itself caused the hospitalizations. Because the chart separated patients into groups with an approximately tenfold difference in risk, it is most useful as a screening aid for identifying patients who require closer assessment of heart function rather than for predicting an individual patient’s risk.
Abstract
Background: Osimertinib is the standard of care for epidermal growth factor receptor mutation-positive non-small cell lung cancer, but heart failure hospitalization (HFH) remains a concern, and no practical tool exists to stratify HFH risk during therapy. Methods: In this retrospective cohort study using a Japanese claims database, 5802 patients newly initiating osimertinib were followed for HFH during treatment. Baseline predictors assessed before the index date were selected by 10-fold cross-validated least absolute shrinkage and selection operator (LASSO) logistic regression and internally validated by bootstrapping (B = 500), repeating predictor selection in each resample. Cumulative incidence functions and Fine–Gray models treated death as a competing event; cause-specific Cox models served as sensitivity analyses. Results: HFH occurred in 169 patients (2.9%) during a median on-treatment follow-up of 9.3 months, with 268 competing deaths. LASSO retained seven predictors. The apparent concordance index (C-index) was 0.731 (95% confidence interval, 0.691–0.771) and the optimism-corrected C-index 0.718. Observed incidence increased 10.2-fold across predicted-risk deciles (1.03–10.50%). Fine–Gray and Cox estimates closely matched the logistic model. Conclusions: Baseline cardiovascular vulnerability stratifies HFH risk during osimertinib therapy. The nomogram, not externally validated, is best used as a screening aid to identify patients who may benefit from intensified cardiovascular monitoring.