OBJECTIVES:

Venous thromboembolism (VTE), including deep venous thromboembolism (DVT) and pulmonary embolism (PE), poses clinical and economic burdens in patients with advanced non-small cell lung cancer (NSCLC). However, little is known about the risk of developing VTE in patients with NSCLC receiving epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). We aim to compare the risk of developing VTE after initiating different EGFR-TKIs in older patients with advanced NSCLC.

METHODS:

Using the 2006-2019 Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified older adults (≥65 years) diagnosed with advanced NSCLC between 2007-2017 and initiated EGFR-TKIs. The predictor variable was the type of EGFR-TKI - 1^st/2^nd generation (gefitinib/erlotinib/afatinib) and 3^rd generation EGFR-TKI (osimertinib). The outcome variable was the incident VTE (DVT, PE). Using propensity score, inverse probability of treatment weighting with 1% trimming was conducted to balance the characteristics of the two groups. Hazard ratio (HR) and 95% confidence interval (CI) were calculated with the Cox proportional hazard model.

RESULTS:

Incidence rate of VTE was higher in 3^rd generation EGFR-TKI group than in 1^st/2^nd generation EGFR-TKIs group. The 3^rd generation EGFR-TKI group had significantly higher risk of VTE with HR of 1.29 (95% CI 1.04-1.61) and PE with HR of 1.32 (95% CI 1.02-1.72) than 1^st/2^nd generation EGFR-TKIs group. The risk of VTE and PE in 3^rd generation EGFR-TKI group compared to 1^st/2^nd generation EGFR-TKIs group appeared even higher in male and white subgroups. The risk of DVT was significantly higher in 3^rd generation EGFR-TKI group than 1^st/2^nd generation EGFR-TKIs group in male subgroup with HR of 4.56 (95% CI 2.01-10.36).

CONCLUSIONS:

Higher VTE and PE risks were observed in patients treated with 3^rd generation EGFR-TKI than those treated with 1^st/2^nd generation EGFR-TKIs, particularly among male and white patients. Careful VTE monitoring would be needed for those populations when using 3^rd generation EGFR-TKI.