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. 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. 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. • Osimertinib cardiac dysfunction ranged from early to ultra-late onset. • Three patients were hospitalized for symptomatic HF with new LVEF decline. • HF therapy stabilized or improved cardiac function in two patients. • Selective osimertinib rechallenge was feasible with close monitoring. • Structured cardiac follow-up is advisable throughout treatment.
Takemura et al. (2026) studied this question.