Targeted therapy‑associated cardiotoxicity in patients with stage‑IV lung cancer with or without cardiac comorbidities

Targeted drugs have revolutionized the treatment of advanced non‑small cell lung cancer (NSCLC). However, the understanding of how cardiac comorbidity and toxicity affect the clinical outcomes of patients following targeted therapy remains limited. In a 14‑year cohort, cardiac comor‑ bidities and toxicities among patients with stage‑IV NSCLC treated with targeted therapy were identified. The cardio‑ toxicities were compared in three patient groups: Cardiac, other and no comorbidities. Survival analysis employed Cox Proportional Hazard Models. In the prospectively followed 3,767 patients with stage‑IV NSCLC, 701 received targeted therapy; of which 133 (19.0%) had cardiac comorbidity, 504 (71.9%) had other comorbidities and 64 (9.1%) had none. In total, 15 patients (2.1%) developed cardiotoxicity after taking drugs targeting epidermal growth factor receptor, anaplastic lymphoma kinase (ALK), c‑ros oncogene 1 (ROS1) or vascular endothelial growth factor/receptor (VEGF)/VEGFR, and all 15 had comorbidities: 10 cardiac and 5 other comorbidities. Cardiac comorbidity was associated with a 7.5‑fold higher risk of targeted therapy‑related cardiotoxicity than other comorbidities (7.5 vs. 1.0%; P<0.001). Patients with or without cardiotoxicity had a median survival time of 4.7 or 1.9 years, respectively, and patients with cardiotoxicity had a lower risk of death (hazard ratio, 0.45; 95% confidence interval, 0.25‑0.81) than those without (P=0.003), when adjusting for comorbidi‑ ties. In the 164 patients that received osimertinib, 32 (19.5%) had cardiac comorbidity and a 1.7‑fold higher risk of death than the 121 (73.8%) patients with other comorbidities. In the 74 patients treated with ALK/ROS1 inhibitors, cardiotoxicity was 14 times more common in patients with heart disease (30.0%) than those without (2.1%) (P=0.001). Cardiotoxicity was uncommon in patients with targeted drug‑treated stage‑IV NSCLC but was more prevalent in those with cardiac comorbidity and appeared to be a protector for longer survival. However, in osimertinib‑treated patients, cardiac comorbidity increased mortality.