Entrectinib-associated perimyocarditis in ROS1-positive NSCLC: a diagnostic and therapeutic dilemma — a case report

Background and clinical significance Entrectinib is an effective therapy for ROS1-positive metastatic non-small cell lung cancer (NSCLC), but rare cardiotoxicity can easily be overlooked due to its non-specific presentation. Case presentation We report the case of a 55-year-old woman with ROS1-positive NSCLC who developed persistent fever and hypotension (85/60 mmHg) after three months of entrectinib, despite achieving excellent tumour regression. Sepsis or neoplastic fever was initially suspected; however, she subsequently developed progressive dyspnoea and acute respiratory failure with rising cardiac biomarkers despite a preserved left ventricular ejection fraction (58%). Multiparametric cardiac magnetic resonance (CMR) findings were consistent with perimyocarditis, and endomyocardial biopsy was not performed. Following drug withdrawal and initiation of therapy for heart failure with preserved ejection fraction (HFpEF) along with colchicine and naproxen for pericardial inflammation, gradual cardiac recovery was achieved, but the tumour rapidly progressed within 13 days (from 22 to 35 mm). Entrectinib was reintroduced at a reduced dose (200 mg daily), yet recurrent cardiopulmonary failure occurred two weeks later, requiring permanent discontinuation. Conclusions This case highlights that entrectinib-associated perimyocarditis can mimic infection, emphasizing the role of advanced non-invasive cardiac imaging, particularly CMR, in establishing the diagnosis. It underscores the profound therapeutic challenge of balancing the life-prolonging benefits of targeted oncological therapy against severe, recurrent cardiotoxicity.