Association between epidermal growth factor receptor–tyrosine kinase inhibitors and venous thromboembolism among older patients with advanced non–small cell lung cancer

Abstract Background Venous thromboembolism (VTE) risk is higher among patients with non–small cell lung cancer (NSCLC) and specific subgroups, including the elderly, but little is known about the VTE risk of different generations of epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR‐TKIs) and whether the risk differs by demographic characteristics. This study aims to compare the risk of VTE (deep venous thromboembolism [DVT]; pulmonary embolism [PE]) between a third‐generation EGFR‐TKI and first/second‐generation EGFR‐TKIs and stratify VTE risk by sex, age, and race/ethnicity in third‐generation EGFR‐TKI users. Methods Via the 2006–2019 Surveillance, Epidemiology, and End Results–Medicare database, this retrospective cohort study included older patients (aged ≥65 years) with advanced NSCLC who initiated on a third‐generation EGFR‐TKI ( n = 493) and first/second‐generation EGFR‐TKIs ( n = 1036). We estimated the hazard ratio (HR) and its 95% confidence interval (95% CI) with the Cox proportional hazards model. Results A third‐generation EGFR‐TKI had a significantly higher VTE risk than first/second‐generation EGFR‐TKIs (HR, 1.26 [95% CI, 1.01–1.57]; p = .037), with an elevated risk in males (HR, 2.16 [95% CI, 1.47–3.19]; p < .001), patients aged ≥75 years (HR, 1.38 [95% CI, 1.04–1.83]; p = .026), and non‐Hispanic Whites (HR, 1.46 [95% CI, 1.10–1.95]; p = .010). Males consistently showed a significantly higher risk of DVT (HR, 2.49 [95% CI, 1.29–4.80]; p = .007) and PE (HR, 2.00 [95% CI, 1.29–3.11]; p = .002). A significantly higher risk of DVT (HR, 1.54 [95% CI, 1.00–2.37]; p = .050) and PE (HR, 1.47 [95% CI, 1.06–2.05]; p = .021) was shown in patients aged ≥75 years and non‐Hispanic Whites, respectively. Among third‐generation EGFR‐TKI users, non‐Hispanic Whites had a significantly higher risk of VTE (HR, 2.04 [95% CI, 1.03–4.02]; p = .041) and PE (HR, 2.88 [95% CI, 1.24–6.70]; p = .014) than non‐Hispanic Asian/Pacific Islanders. Conclusions Close monitoring of VTE events in high‐risk patients is essential to promote early diagnosis and treatment.