Emerging evidence suggests that DOACs are likely to replace low molecular weight heparin as the standard of care for cancer-related thrombosis, with the possible exception of patients with GI cancer, an international experts says.

Speaking at the Blood 2019 meeting in Perth, Professor John Eikelboom, a haematologist from McMaster University in Canada, told delegates that venous thromboembolism was a huge problem in cancer patients.

“We know that VTE has an incidence of somewhere between 1 to 3/1000 per year … active cancer accounts for about 20 per cent of all VTE so it is a big problem and it’s challenging to treat,” he told delegates.

He noted that the risk of VTE varies with the natural history of cancer as well as the type of cancer.

“Some cancers have a much higher risk of VTE than others, including pancreatic cancer, cancer involving the brain, lung cancer, GI and ovarian cancer,” he said.

A role in primary prevention?

A lack of evidence for benefit meant that routine thromboprophylaxis in medical cancer patients was not recommended by European or US guidelines, Prof. Eikelboom noted.

However, he suggested it was reasonable to use primary prevention in selected high-risk groups.

“If you have a patient with pancreatic cancer who has an annual VTE risk of 20 percent it may well be very sensible to put them on a low dose of rivaroxaban or apixaban… but you won’t save lives and there will be a risk of a cost to pay in terms of bleeding,” he said.

LMWH the current standard of care for secondary prevention

Prof. Eikelboom noted that the current standard of care for the treatment of cancer related VTE was low molecular weight heparin.

The international CLOT trial involving Australia changed practice around the world because a simple randomisation with LMWH as an alternative to warfarin reduced the risk of VTE recurrence by one half.

“The NNT in this trial was only 13 it is sobering that despite halving the risk of VTE there is no impact on survival. I recognise that the trial was not designed to show a survival impact but if VTE in cancer is such a powerful predictor of death why aren’t we saving lives? To me this is one of the curiosities of this whole field,” Prof. Eikelboom said.

But according to Prof. Eikelboom, LMWH was not the answer because of several challenges with its use.

“There is still a significant risk of breakthrough events, subcutaneous injections are not always pleasant and so there is a substantial attrition rate over time and of course we don’t know what to do after 6 months because the CLOT trial did not go beyond this [time point],” he said.

Are DOACS the answer?

Prof. Eikelboom told delegates that the results of trials comparing DOACs and LMWH were very encouraging.

The Hokusai-VTE Cancer Study compared an initial 5 days of dalteparin followed by edoxaban with dalteparin, and SELECT-D study compared rivaroxaban with dalteparin, in patients with cancer related thrombosis.

Both trials demonstrated non-inferiority of DOAC compared with LMWH for the composite outcome of recurrent venous thromboembolism or major bleeding however excess GI bleeding was noted.

“When this was further explored the excess bleeding appeared to be confined to one particular subgroup and that was the patients with GI cancer,” he said.

“Based on these results, DOACs are likely to replace LMWH as the standard of care for cancer-related thrombosis, with the possible exception of patients with GI cancer,” he added.

A number of questions remain 

According to Prof. Eikelboom there were still many unresolved issues in cancer-related thrombosis, mainly:

• If VTE is such an important cause of death, why can’t we demonstrate survival benefits?
• What is the optimal duration of management?
• What is the optimal management of recurrent VTE despite therapeutic anticoagulation?
• How should we manage arterial thrombosis e.g MI, stroke?
• How should we manage incidental thrombosis?
• How should we manage thrombosis in patients with low platelets treatment due to their cancer or cancer treatment?