Extended anticoagulation benefits cancer patients with distal DVT

In cancer patients with isolated distal deep vein thrombosis (IDDVT), a 12-month anticoagulation regimen with the oral factor Xa inhibitor edoxaban fared better than a 3-month regimen, findings from the ONCO DVT study have shown.

“Within 3 months, the incidence of the primary endpoint was quite low in both groups – it was only about 1 percent,” said principal investigator Dr Yugo Yamashita from Kyoto University, Japan, in a Hot Line session at ESC 2023. “After 3 months, the incidence in the 12-month group remained low but increased gradually in the 3-month group. The between-group difference was statistically significant.”

The incidences of symptomatic recurrent venous thromboembolism (VTE) or VTE-related death in the 12- and 3-month arms were 1.2 percent and 8.5 percent, respectively. The odds ratio (OR) was 0.13; log-rank p value was <0.001. [ESC 2023, Hot Line 9 session]

Albeit lacking statistically significant differences, the 12-month edoxaban regimen still trumped the 3-month regimen on subgroup analyses.

“[Our findings] successfully demonstrated the superiority of 12-month edoxaban compared with 3-month treatment in terms of the primary endpoint,” Yamashita said.

 

Major secondary endpoint

Major bleeding rate was slightly higher with 12 vs 3 months of edoxaban therapy, but the between-group difference failed to achieve statistical significance (10.2 percent vs 7.6 percent; OR, 1.34).

Despite the higher rate with the 12-month regimen, most of the patients in this group were receiving a low dose of the study drug, noted discussant Dr Teresa López-Fernández from the La Paz University Hospital, Madrid, Spain. “The risk of bleeding is not the same in all cancer types. This is an important point to bear in mind when translating the data in clinical practice.”

 

Common in cancer patients

“IDDVT is very common in cancer patients. It is a more benign condition compared with proximal DVT. However, the risk of recurrence is not low,” Yamashita said.

Guidelines recommend prolonged anticoagulation in IDDVT patients when active cancer exists, particularly among those with metastatic disease. [Chest 2021:160:e545-e608; Eur Heart J 2022;43:4229-4361; Ann Oncol 2023;34:452-467] However, trials on DDVT patients excluded those with active cancer.  [Lancet Haematol 2016;3:e556-e562; BMJ 2022;379:e072623]

Yamashita and his team thus conducted this investigator-initiated superiority trial to determine which treatment duration would benefit more in this patient setting. A total of 601 patients (mean age 71 years, ~70 percent female) with active cancer who had a new diagnosis of IDDVT were randomized 1:1 to 3 or 12 months of anticoagulation therapy with edoxaban. The study drug was administered orally at 60 or 30 mg daily based on reduced dose criteria.

About 2 percent of the total cohort were lost to follow-up. Baseline characteristics were well balanced between arms. About 25 percent of participants had metastatic disease. The most frequent cancer sites were the ovaries (14 percent) and uterus (13 percent). “Our study population reflected typical cancer patients with DVT in daily clinical practice,” said Yamashita.

Nearly 90 percent of patients on the 3-month regimen had stopped edoxaban by day 120, but even in the 12-month group, a certain number of patients discontinued edoxaban prematurely, Yamashita noted. By day 360, persistent edoxaban discontinuation* rate in the 12-month arm was 41 percent.

 

Implications

Cancer-associated IDDVT is a marker for poor prognosis. In cancer patients, risk factors for both VTE and bleeding (eg, cancer type, stage, treatment; weight; VTE and bleeding history; potential drug-drug interactions, among others) should be taken into context in treatment planning, López-Fernández noted.

“ONCO DVT supports the indication for extended anticoagulation in cancer patients with IDDVT,” said López-Fernández.

“This is the first and only randomized trial to show superiority of longer over shorter duration of anticoagulation therapy for reducing thrombotic events in cancer patients with IDDVT. We expect that the results will change practice and clinical guidelines in the cardio-oncology field,” Yamashita concluded.