PB0969 - Treatment of cancer associated venous thromboembolism with apixaban in patients receiving concomitant TAXANES.

Background: The Taxanes (paclitaxel, docetaxel and cabazitaxel) are systemic anti-cancer therapies (SACT) that undergo extensive hepatic metabolism in the liver by the cytochrome P450 isoenzyme 3A4 (with some reports of additional CYP3A4 induction activity). Taxanes are also transported via P-glycoprotein (P-gp) and have the potential to interact with DOACs such as apixaban.

Aims: Describe the effect of Taxane SACT on anticoagulant efficacy and safety of apixaban treatment of cancer associated venous thromboembolism (CAT).

Methods: Consecutive CAT patients on Taxane SACT and prescribed apixaban were followed up for a period of 12 months (or until death whichever occurred earlier) to describe VTE recurrence / bleeding episodes. Patients prescribed therapeutic dose apixaban also had a trough plasma level measured.

Results: 11 patients received concomitant apixaban and taxane treatment (6 on apixaban 5mg bid and 5 on 2.5mg bid). Patients were predominately female (8/11) with a mean age of 65 (range 51-80). Trough apixaban levels were recorded for all patients on apixaban 5mg bid and for three of five patients on 2.5mg bid (see table 1). All trough levels were above the 5th centile of predicted exposure reported in the summary of product characteristics (SPC). One patient who was also receiving nintedanib a tyrosine kinase inhibitor (TKI) and additional CYP3A4 substrate and P-gp inhibitor, had a trough level above the predicted 95th centile. No on treatment clinically significant major or non-major bleeding was observed. One of 11 patients suffered a VTE recurrence, and 2 (18%) patients died during the 12-month follow-up period.

Conclusion(s): No evidence of plasma level drug-drug interaction between the taxanes and apixaban. Co-administration of taxanes and apixaban in patients treated for CAT did not result in any additional bleeding events. The VTE recurrence rate of 9% (1 out of 11) is consistent with the expected VTE recurrence rate in patients with cancer and SACT.