Industry-funded trial finds a direct factor X inhibitor noninferior to a low-molecular-weight heparin for cancer-associated VTE

The oral direct factor X inhibitor edoxaban appeared noninferior to the subcutaneous low-molecular-weight heparin (LMWH) dalteparin for preventing venous thromboembolism (VTE) in patients with cancer, an industry-funded trial has found.

Researchers performed an open-label noninferiority trial in which patients with cancer and acute symptomatic or incidental VTE were randomly assigned to edoxaban or dalteparin. According to the study protocol, patients' treating physicians were required to initially intend to administer LMWH for a minimum of six months. Patients in the edoxaban group received LMWH for at least five days followed by oral edoxaban, 60 mg once daily, while those in the dalteparin group received subcutaneous dalteparin, 200 IU per kg of body weight once daily, for one month, then dalteparin, 150 IU per kg once daily. Treatment was administered for a minimum of six months and for a maximum of 12 months. The primary outcome of the study, which was funded by Daiichi Sankyo, was a composite of recurrent VTE or major bleeding in the 12 months after randomization, independent of duration of treatment. The results were published online Dec. 12 by the New England Journal of Medicine.

Overall, from July 2015 through December 2016, 1,050 patients were randomized to a treatment group and 1,046 were included in a modified intention-to-treat analysis, 522 in the edoxaban group and 524 in the dalteparin group. All patients were followed for 12 months or until the trial ended and were assessed in the clinic or by phone on day 31 after study randomization and at months 3, 6, 9, and 12. Sixty-seven patients in the edoxaban group had a primary outcome event versus 71 patients in the dalteparin group (12.8% vs. 13.5%; hazard ratio, 0.97; P=0.006 for noninferiority). Forty-one patients in the edoxaban group and 59 patients in the dalteparin group had recurrent VTE (7.9% vs. 11.3%; hazard ratio, 0.71; P=0.09), while major bleeding occurred in 36 and 21 patients, respectively (hazard ratio, 1.77; P=0.04). Two hundred six patients in the edoxaban group and 192 patients in the dalteparin group died (39.5% vs. 36.6%), most due to cancer-related causes. In each group, six deaths were related to VTE or to bleeding.

The researchers noted that their trial was limited by its open-label design, by the lower-than-expected number of primary outcome events, and by the fact that the median duration of treatment was shorter for dalteparin than edoxaban. They also pointed out that they could not make definitive conclusions about outcomes by type of tumor. However, they concluded that in their trial, edoxaban was noninferior to dalteparin for a composite outcome of recurrent VTE or major bleeding. When the outcomes were considered separately, edoxaban was associated with a lower rate of recurrent VTE but a higher rate of major bleeding.