Pharmacokinetics of edoxaban in EGFR-mutated non-small cell lung cancer patients with venous thromboembolism.

Abstract

The risk of venous thromboembolism (VTE) is increased 7-fold in patients with cancer than in those without. Low-molecular-weight heparin is the standard treatment for cancer-associated VTE. Direct oral anticoagulants (DOACs) are not inferior to low-molecular-weight heparin with respect to the general outcome of recurrent VTE. Warfarin is associated with a risk of bleeding when used in combination with gefitinib or erlotinib which are epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). It is unclear, however, whether combination treatments with EGFR-TKIs and DOACs pose the same risk. We aimed to identify anticancer drugs and anticoagulants that can be used safely in combination, as accompanying research to an observational study on VTE incidence rates in lung cancer patients (Rising-VTE/NEJ037 study). Twelve patients receiving EFGR-TKI monotherapy and VTE treatment were enrolled. Blood samples were collected in time series after the first dose of edoxaban, and further samples were collected within 8-15 days after administering EGFR-TKIs. The pharmacokinetics (PK) of edoxaban were analyzed using a non-compartmental model. Edoxaban concentrations (30mg once daily) were measured in eight patients. PK analyses showed no significant differences before and after co-administration of EGFR-TKIs (gefitinib, erlotinib, and afatinib). Our findings indicate that the PK of edoxaban was not considerably affected by co-administration of EGFR-TKIs (gefitinib, erlotinib, and afatinib).