Edoxaban Likely Prevents VTE Recurrence in Patients With Lung Cancer, Despite High Rates of Bleeding

Many clinicians who manage patients with advanced lung cancer have frequently observed high rates of venous thromboembolism (VTE), but neither the incidence of VTE in this population nor the efficacy of the direct oral anticoagulant edoxaban for prevention has been well documented to date.

Research presented at the 2021 ASCO Annual Meeting by Yukari Tsubata, MD, PhD, of Shimane University Hospital in Izumo, Japan, however, demonstrates a high cumulative incidence of VTE in patients with advanced lung cancer. The use of edoxaban in these patients helped prevent VTE recurrence over six months, but the therapy was associated with bleeding events and did not seem to improve survival substantially.

In patients with cancer, VTE is an important cause of morbidity and mortality. The increased risk of VTE is highest during the first few months following diagnosis, Dr. Tsubata and coauthors noted. The risk of recurrence must also be considered, as this can persist for several years following an initial symptomatic VTE episode.

The multicenter Rising-VTE/NEJ037 study included 1,008 patients with lung cancer ineligible for radical resection or radiation. Patients in the overall cohort were followed for newly diagnosed VTE; patients who experienced a VTE were prescribed edoxaban and were then followed for VTE recurrence in the subsequent six months.

Most of the population was male (70.8%) and the median age was 70 years (range = 30-94).

Approximately 86% of patients presented with non-small cell lung cancer, while 14% had small cell lung cancer. The histological types of cancer were adenocarcinoma (63.6%), squamous cell carcinoma (18.6%), and “other” (4.2%).

In total, 104 patients (10.3%) developed VTE – 62 (6.2%) at the time of lung cancer diagnosis and 42 (4.2%) during the follow-up period.

The investigators observed no recurrent VTE cases within the six months following edoxaban initiation. Although this finding indicated treatment with edoxaban was likely effective at preventing short-term VTE recurrence, the therapy was associated with major and minor bleeding events in 23% of patients.

Six of the 1,008 patients died as a result of major bleeding, but no deaths due to bleeding were reported in the edoxaban-treated group. The authors also reported that there was no statistically significant difference between the non-VTE and the edoxaban-
treated VTE groups in terms of the two-year survival probability (0.43 vs. 0.48, respectively).

In a multivariable analysis, the investigators found that female sex, adenocarcinoma, poor performance status score, a history of myocardial infarction, and decreased platelet count were associated with VTE. “We are planning to analyze the relationship between driver gene mutations and VTE risk in more detail and to create a predictive nomogram of VTE onset specific to lung cancer,” the authors concluded.

Study authors report relationships with Daiichi Sankyo, the manufacturer of edoxaban.


Tsubata Y, Hotta T, Hamai K, et al. Incidence of venous thromboembolism in advanced lung cancer and efficacy and safety of direct oral anticoagulant: A multicenter, prospective, observational study (Rising-VTE/NEJ037 Study). Abstract #12021 presented at the 2021 American Society of Clinical Oncology Annual Meeting, June 4-8, 2021.