Exploring therapeutic drug monitoring-guided direct oral anticoagulant use in patients with non-small cell lung cancer treated with small-molecule inhibitors

ABSTRACT Background Patients with advanced non-small cell lung cancer are at increased risk of venous thromboembolism (VTE) and often receive direct oral anticoagulants (DOACs) for thromboprophylaxis. Using oral anticancer small-molecule inhibitors (SMIs) concurrently may affect bleeding or thrombotic risk by altering DOAC pharmacokinetics. However, data on safety of concomitant use and the relevance of therapeutic drug monitoring (TDM) in this setting are limited. Methods Using pooled data from a prospective study and routine care, we evaluated DOAC pharmacokinetics and incidence of thromboembolic and clinically relevant bleeding (CRB) events during TDM-guided DOAC management in patients receiving SMIs. Patients were included if they had at least one steady-state DOAC peak or trough concentration measured during SMI treatment. DOAC concentrations were reported to the treating physician, who could adjust anticoagulant therapy at their discretion. Results DOAC concentrations outside the expected on-therapy range occurred in 17/48 patients; none were observed with osimertinib (0/13), whereas elevated exposure occurred more frequently with alectinib (5/9). During median follow-up of 11.9 (range: 0.3-48.8) months, no VTEs were observed, two strokes, and seven CRB events (of which three trauma-related). Two CRB events occurred during elevated DOAC exposure prior to DOAC adjustment. No bleeding or thromboembolic events were observed following DOAC dose adjustment or switching. Conclusions While underpowered for subgroup analyses, our findings suggest that specific SMIs predispose to deviant DOAC exposure. TDM-guided management effectively restored DOAC exposure to within expected on-therapy ranges. Prospective validation is needed to assess whether this strategy can reduce bleeding and thromboembolic risk.