Incidence of venous thromboembolism in advanced lung cancer and efficacy and safety of direct oral anticoagulants: a multicenter, prospective, observational study (Rising-VTE/NEJ037 study)

Abstract

Background: Venous thromboembolism (VTE) is a well-known type of cancer-associated thrombosis and a common complication of malignancy. However, the incidence of VTE associated with lung cancer and the effectiveness of direct oral anticoagulants remain unclear. This study aimed to identify the incidence of VTE associated with lung cancer at the time of diagnosis or during treatment, the efficacy and safety of edoxaban, and associated risk factors. Methods: The Rising-VTE/NEJ037 study was a multicenter prospective observational study. Altogether, 1021 patients with lung cancer who were unsuitable for radical resection or radiation were enrolled and followed up for 2 years. Patients with VTE at the time of lung cancer diagnosis started treatment with edoxaban. The primary endpoint of this trial was the rate of newly diagnosed VTE after enrollment or recurrence rate 6 months after treatment initiation. Results: Data were available for 1008 patients. The median age was 70 years (range: 30–94 years), and 70.8% were men. Sixty-two patients had VTE at the time of lung cancer diagnosis, and 38 (9.9%) developed VTE at follow-up. No cases of VTE recurrence were recorded 6 months after treatment initiation with edoxaban. Major and clinically relevant non-major bleeding events occurred in 4.9% of patients and increased to 22.7% in the edoxaban treatment group. Conclusions: VTE occurrence should be monitored during lung cancer treatment. Although treatment with edoxaban was highly effective in preventing VTE recurrence, its administration should be cautiously considered because of the high bleeding rate. Trial registration: jRCTs061180025.

Identification of risk factors for venous thromboembolism and validation of the Khorana score in patients with advanced lung cancer: based on the multicenter, prospective Rising-VTE/NEJ037 study data

“…The most common histological lung cancer subtypes were adenocarcinoma (641 patients, 63.6%). The disease stage was assessed according to the 7th edition TNM staging system for lung cancer (UICC-7) [ 18 ]; the M1a,b stage IV disease accounted for 80% of all cases [ 16 ]. Overall, 62 and 38 patients had VTE at lung cancer diagnosis and over the two years of follow-up, respectively, totaling 100 VTE cases.…”

“…The Rising-VTE/NEJ037 study is the largest prospective study to intensively screen patients for VTE at lung cancer diagnosis, monitor their subsequent progression, and determine the incidence rate of VTE [ 16 ]. The rate of VTE co-development over 2 years of follow-up was 9.9%.…”

“…Patients who met the Rising-VTE/NEJ037 study eligibility criteria underwent evaluations for VTE co-development by contrast-enhanced computed tomography (CT) scans of the chest to the lower extremities or of the chest to the pelvic CT, along with lower-extremity venous ultrasound. Furthermore, patients were classified into either the observation group without VTE co-development or the cancer-associated VTE group [ 16 ]. VTE diagnoses were confirmed through a central review by two radiologists.…”

“…The Rising-VTE/NEJ037 study, a physician-led, multicenter, prospective, observational study, determined the incidence rate of VTE and its risk factors while treating lung cancer patients for whom radical treatments were unsuitable [ 16 ]. To the best of our knowledge, the Rising-VTE/NEJ037 study is the largest prospective study involving intensive screening for VTE at the time of lung cancer diagnosis, along with a further follow-up, to assess VTE incidence.…”

Pulmonary Thromboembolism Developed During Hospitalization: A Nationwide Retrospective Observational Study Using Claims Data

“…The incidence of VTE in patients with cancer is 4–7 times higher than that in patients without cancer [ 14 , 15 ]. The risk of VTE development differs according to cancer type, with lung cancer showing one of the highest risks among all cancer types [ 16 ], with 5–6% of patients with lung cancer having VTE in Japan [ 17 , 18 ]. The high incidence of VTE in patients with cancer could be attributed to increased coagulation activities due to humoral factors produced by cancer cells and surrounding tissues, endothelial cell damage caused by chemotherapy and other anticancer treatments, surgical cancer treatment, decreased physical activity, and advanced age [ 19 ].…”