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AMSTERDAM -- A prolonged course of edoxaban (Savaysa) was more effective for isolated distal deep vein thrombosis in cancer patients, the ONCO DVT randomized trial showed.

By 12 months, symptomatic recurrent venous thromboembolism (VTE) or VTE-related death was less likely in patients assigned to 12 months versus 3 months of the direct oral anticoagulant (DOAC; 1.2% vs 8.5%, OR 0.13, 95% CI 0.03-0.44).

There was no significant jump in bleeds with prolonged anticoagulation, as the rate of International Society on Thrombosis and Hemostasis-defined major bleeding reached 10.2% after 12-month edoxaban versus 7.6% after the 3-month regimen (OR 1.34, 95% CI 0.75-2.41), reported Yugo Yamashita, MD, of Kyoto University Graduate School of Medicine in Japan, during the European Society of Cardiology (ESC) Congress.

The study was also published in .

VTE blood clots are one of the most important complications of cancer therapy, developments for which have allowed many more cancer patients to survive in recent years and birthed the burgeoning field of cardio-oncology.

In daily practice, isolated clots in the infrapopliteal veins (without coexisting proximal DVT or pulmonary embolism) are a very common finding in cancer patients, and it had been unclear if this isolated distal DVT is truly less benign than a proximal DVT, Yamashita told the ESC audience.

Based on ONCO DVT, cancer-associated isolated distal DVT is a marker for poor prognosis and supports an indication for extended anticoagulation in affected patients, said session discussant Teresa López Fernández, MD, of La Paz University Hospital in Madrid.

U.S. and European guidelines alike weakly recommend anticoagulation of prolonged duration in these cancer patients due to the lack of randomized data.

In the trial, more than half of recurrent VTE events by 12 months were recurrent distal DVTs, with fewer pulmonary embolisms with hypoxia and proximal DVTs. "The clinical relevance of recurrent distal DVT might be lower than that of recurrent proximal DVT, whereas development of recurrent distal DVT with symptoms could lead to additional anticoagulation therapy," the study investigators surmised.

"When physicians consider the potential benefit of extended anticoagulation therapy beyond 3 months, it should be taken into consideration that most of the favorable effects could be based on the prevention of recurrent distal DVT," they wrote.

López Fernández highlighted the need to better protect patients at high risk of bleeding, acknowledging that the decision to stop or continue anticoagulation depends on many characteristics and it is difficult to assess an individual's global bleeding risk.

She pointed out that fully three-quarters of the trial participants received low-dose edoxaban (30 mg instead of 60 mg daily) due to a creatinine clearance of 30-50 mL/minute or a body weight of 60 kg or less -- suggesting their bleeding risk may not be comparable to other populations.

More research is needed into other DOACs, other dosing schemes, and other patients with high risk of bleeding, she suggested.

ONCO DVT was an open-label trial with blinded adjudicators conducted at 60 centers across Japan. Participants had active cancer and were newly diagnosed with an isolated distal DVT confirmed by whole-leg ultrasonography; those already on anticoagulation therapy or with a pulmonary embolism were excluded.

There were 604 cancer patients randomized to 12- or 3-month edoxaban treatment, 601 of whom were included in the intention-to-treat analysis after a few withdrew consent.

Groups were well balanced at baseline. Mean age was 71 years, and 28% were men. One in five had DVT symptoms, and a quarter had metastatic disease. Cancers represented in the cohort were gynecologic cancers (28%), lung cancer (11%), colon cancer (10%), and others.

Yamashita said that subgroup analysis showed no interactions in the primary treatment effect by age, sex, body weight, history of VTE, creatinine clearance, platelet count, anemia, edoxaban dose adjustment, history of major bleeding, and cancer metastasis.

One caveat of the ONCO DVT trial was the substantial discontinuation of edoxaban due to bleeding events and cancer progressions in the 12-month group, who ended up with a 20% rate of premature discontinuations at 120 days.

Yamashita also acknowledged other study limitations, such as lower-than-expected event rates, and the uncertain generalizability of the study results to non-Asian populations and other cancer types.

"Not all patients should receive prolonged anticoagulation," he noted, urging caution for those with high risk of bleeding.

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