Gefitinib-Induced Heart Failure Confirmed by a Rechallenge in a Patient with EGFR-Mutated Lung Adenocarcinoma

An 84-year-old woman with epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma developed sequential cardiotoxicity during treatment with two EGFR tyrosine kinase inhibitors. Osimertinib induced QT prolongation without systolic dysfunction, thus necessitating discontinuation. After switching to gefitinib, the patient developed heart failure with a reduced ejection fraction, which resolved after drug withdrawal, but recurred upon rechallenge. This case represents a rare instance of severe gefitinib-induced heart failure following electrical instability associated with osimertinib and highlights the need for careful cardiac monitoring and the awareness of cumulative cardiotoxicity when switching EGFR tyrosine kinase inhibitors, even to first-generation agents which are considered to be safe.