Servier Canada announced results from the Hokusai-VTE CANCER study evaluating oral edoxaban and found that edoxaban is non-inferior to subcutaneous injectable LMWH dalteparin for the treatment of cancer-associated VTE or major bleeding.
The Hokusai-VTE CANCER study met the primary objective of non-inferiority of edoxaban for the composite outcome of first recurrent VTE or ISTH-defined major bleeding during a 12-month study period, which occurred in 67 of 522 patients (12.8%) in the edoxaban group compared with 71 of 524 patients (13.5%) in the dalteparin group (hazard ratio with edoxaban, 0.97; 95% CI, 0.70 to 1.36; P = 0.006 for non-inferiority) for a risk difference (edoxaban minus dalteparin) of -0.7% (95% CI, -4.8 to 3.4). The difference in risk for recurrent VTE was -3.4% (95% CI, -7.0 to 0.2) whereas the corresponding difference in risk for major bleeding was 2.9% (95% CI, 0.1 to 5.6). The frequencies of severe major bleeding events at presentation (categories 3 and 4) were similar during treatment with edoxaban or dalteparin (12 patients in each group, respectively). There was no fatal bleed in the edoxaban group versus two fatal bleedings in the dalteparin arm.
The study also met the secondary outcome of event-free survival (free of recurrent VTE, major bleeds or death) at 12 months, and rates were similar between edoxaban and dalteparin (55.0% and 56.5%, respectively). The trial was a PROBE design study and included a broad spectrum of patients (n=1,050) with primarily active cancer; (98%), 53% of which had metastatic cancer and 72% of which were receiving cancer therapy at randomization.
"Cancer patients with venous thromboembolism are at increased risk of both recurrent venous thromboembolism and bleeding compared with patients without cancer. Both of these complications can delay cancer treatment and necessitate hospitalization. Therefore, both are important. This trial shows that oral edoxaban is as effective as the standard of care, subcutaneous dalteparin. Although there is more major bleeding with edoxaban, there is no increase in serious bleeding. Therefore, our cancer patients with venous thromboembolism now have an oral treatment alternative to subcutaneous dalteparin," said member of the executive committee of the HOKUSAI-VTE Cancer trail, Dr. Jeffrey Weitz, MD, Professor of Medicine and Biochemistry at McMaster University and Executive Director of the Thrombosis and Atherosclerosis Research Institute in Hamilton, Ontario.
VTE includes both deep vein thrombosis (DVT) and pulmonary embolism (PE) and is the second leading cause of death in cancer patients receiving chemotherapy. The treatment of cancer-associated VTE is challenging because these patients are at increased risk of both recurrent VTE and major bleeding. The occurrence of VTE increases the risk of death 2-6-fold in cancer patients and can interrupt cancer treatment.