Osimertinib-associated cardiac dysfunction in epidermal growth factor receptor-mutant non-small cell lung cancer: a single-center three-case series requiring hospitalization.

Background: Osimertinib is frequently used for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), whereas cardiotoxicity signals, including left ventricular ejection fraction (LVEF) decline, heart failure (HF), and corrected QT interval prolongation, have been documented. Cases: We describe three patients without clinical HF at baseline who were hospitalized for symptomatic HF with newly documented LVEF decline during osimertinib therapy. Case 1 (a 61-year-old woman with prior anthracycline exposure) developed early HF at approximately 1 to 2 months. Recovery was incomplete despite discontinuation and guideline-directed HF therapy, and she died at approximately 10 months after HF onset owing to cancer progression. Case 2 (a 72-year-old woman) presented at 12 months. Osimertinib was continued under HF therapy, and LVEF recovered. Case 3 (a 74-year-old woman; fourth-line osimertinib) presented at 60 months (ultra-late). Following a 2-month interruption and HF therapy, osimertinib was reintroduced without recurrence, and LVEF recovered. Conclusion: These cases illustrate that osimertinib-associated cardiac dysfunction can develop from early to ultra-late phases and that selective rechallenge may be considered following HF therapy optimization and recovery with close monitoring. Comparative risk or incidence was not evaluated.