Patients with active cancer and newly diagnosed isolated distal deep vein thrombosis (DVT) who received 12 months of edoxaban (Savaysa) had fewer thrombotic events at 1 year than those who received 3 months of treatment, without significantly increased bleeding, in the ONCO-DVT trial.
However, lead author Yugo Yamashita, MD, of Kyoto University noted that caution is needed when determining anticoagulation strategies in individual patients with distal DVT, especially those with high risk for bleeding.
Dr. Yamashita presented the results at the annual congress of the European Society of Cardiology, and the trial was simultaneously published in the journal Circulation.
“This is the first and only randomized trial to show the superiority of longer duration over shorter duration of anticoagulation therapy for reducing thrombotic events in cancer patients with isolated distal DVT,” he said in a press briefing.
The results provide support for 12 months of edoxaban in patients with active cancer and isolated distal DVD, he said in an email.
However, “considering the risk of bleeding associated with anticoagulation therapy, physicians should make the decision of anticoagulation strategies for these patients based on risk-benefit balance of anticoagulation therapy in individual patients,” he stressed.
The take-home message for clinicians is that, “if you find minor DVT in cancer patients, please be careful, because their thrombotic risk was not low” in this trial, Dr. Yamashita said.
The study was conducted in Japan, so whether or not the results are generalizable to other populations is not clear. “Subgroup analysis based on body weight did not show any signal of different effect,” he noted, which suggests that the main results could be applied to other populations, including the U.S. population. However, “generalizability of the current results should be carried out carefully.”
Caution needed when translating findings into clinical practice
The assigned discussant, Teresa Lopez-Fernandez, MD, from La Paz University Hospital, Madrid, who was co-chairperson of 2022 ESC guidelines on cardio-oncology, noted that the optimal anticoagulation therapy strategy is unclear in patients with cancer and isolated distal DVT.
“2022 ESC guidelines on cardio-oncology and [European Society for Medical Oncology] guidelines from this year,” she said, “are both in agreement that we need to prolong anticoagulation [therapy to prevent venous thromboembolism (VTE)] when active cancer exists, and particularly in patients with metastatic cancer. The problem is that none of this text refers specifically to distal DVT.”
The ONCO-DVT trial sheds light on this, but there are a few points to consider when interpreting the findings.
Major bleeding was slightly increased in the 12-month vs 3-month edoxaban groups, although this was not statistically significant, she noted. Moreover, 75% of the patients were treated with low-dose edoxaban, mainly due to their low weight. Also, bleeding risk probably differs in different cancer types.
“These are important things that we need to keep in mind when we try to transfer this data to [inform] our clinical practice,” Dr. Lopez-Fernandez said.
She drew attention to a recent study based on RIETE registry data that suggests that “isolated distal DVT is a big problem for patients with cancer in comparison with noncancer patients, where it seems it’s a low-risk problem.”
The main takeaways from ONCO-DVT, Dr. Lopez-Fernandez said, are that it confirms that cancer-associated isolated distal DVT is a marker of poor prognosis, and it supports the need for extended anticoagulation in patients with active, ongoing cancer and isolated distal DVT.
However, “we need to be cautious to try to really understand what the bleeding risks of these patients are,” she said, “particularly because it is not always easy to transfer the results from an Asian population to other populations.”
There is also a need for further studies with other doses, with other novel oral anticoagulants, and in patients at high risk for bleeding, in clinical practice.
Dr. Yamashita said that the study suggests that there is a potential benefit of prolonged duration of anticoagulant therapy for some patients with isolated distal DVT, but not all patients should receive this dosing strategy, because some patients may be at high risk for bleeding or VTE recurrence. A subanalysis of data from ONCO-DVT study should shed further light on this.
“We need to individualize our risk stratification,” Dr. Lopez-Fernandez said, adding that notably, “a lot of patients in the 12-month group did not continue with the 12-month treatment,” which may have affected bleeding results. Dr. Yamashita agreed.