The noninferiority of edoxaban compared with dalteparin in preventing recurrent venous thromboembolism (VTE) and major bleeding in patients with cancer highlights edoxaban as a potential alternative to low molecular weight heparin (LMWH) in this group of patients, suggests results of the Hokusai VTE-Cancer Study presented at ASH 2017.

According to study lead author Professor Gary E. Raskob from the University of Oklahoma College of Public Health, Oklahoma City, Oklahoma, US, major guidelines (eg, ASCO*, ESMO**) currently recommend the use of subcutaneous LMWH to treat VTE. However, subcutaneous injections may be burdensome and lead to treatment discontinuation, making direct oral anticoagulants a more attractive choice in these patients.

“For the vast majority of patients with cancer-associated VTE, treatment with oral edoxaban can replace the injectable dalteparin,” said Raskob.

In this multicentre (114 sites in North America, Europe, Australia, and New Zealand), open-label, blinded outcome trial, 1,050 patients with cancer and VTE were randomized 1:1 to the LMWH dalteparin (200 IU/kg reduced to 150 IU/kg on day 30; n=524) or 5 days of LMWH followed by oral edoxaban (60 mg QD; n=522) for at least 6 months and up to 12 months.

Incidence of the primary composite outcome (first recurrent VTE or major bleeding event) was comparable between patients on edoxaban and dalteparin in the primary analysis (12.8 percent vs 13.5 percent; hazard ratio [HR], 0.97, 95 percent confidence interval [CI], 0.70–1.36; p=0.006). The incidence of the primary outcome was also similar between groups at 6 months in a sensitivity analysis (10.5 percent vs 10.7 percent; HR, 1.01, 95 percent CI, 0.69–1.46; p=0.018). [ASH 2017, abstract LBA-6]

There was a lower rate of recurrent VTE among patients on edoxaban vs dalteparin (6.5 percent vs 10.3 percent; -3.8 percent absolute risk difference), and a higher rate of major bleeding events (6.3 percent vs 3.2 percent; 3.1 percent absolute risk difference).

The elevated rate of major bleeding was driven primarily by the higher number of upper gastrointestinal bleeds in patients on edoxaban compared with dalteparin (n=17 vs 3) and mostly affected patients who had gastrointestinal cancers at study entry, said Raskob.

The incidence of category 3 and 4 bleeding (life-threatening emergency and fatal bleeding, respectively) was comparable between patients on edoxaban and dalteparin (2.3 percent in each group), as was event-free survival at 12 months (55.0 percent vs 56.5 percent).

“Treatment of cancer-associated VTE is challenging because the risk of recurrence and bleeding complications with treatment are both higher in cancer patients than in noncancer patients. Both of these complications … contribute to morbidity and mortality but importantly, for oncologists, they may interfere with … definitive anticancer therapy to the patients,” said Raskob.

“Preventing VTE recurrence and major bleeding can allow the oncologist to really focus on the patient’s cancer treatment,” he said, suggesting that the lower rate of recurrent VTE as observed among patients on edoxaban can be offset by a similar increase in major bleeding risk.

“A huge question is whether or not to use direct oral anticoagulants in patients with cancer … but the studies just hadn’t been done. This is practice-changing,” said Professor Robert Brodsky from the Johns Hopkins School of Medicine in Baltimore, Maryland, US who moderated the ASH 2017 late-breaking abstract session.