Treatment of cancer‐associated venous thromboembolism: 12‐month outcomes of the placebo versus rivaroxaban randomization of the SELECT‐D Trial (SELECT‐D: 12m)

Abstract

Background The Anticoagulation Therapy in Selected Cancer Patients at Risk of Recurrence of Venous Thromboembolism (SELECT‐D) trial demonstrated reduction in recurrent venous thromboembolism (VTE) but increased bleeding with rivaroxaban compared with dalteparin for treatment of acute VTE in cancer patients, at 6 months. Uncertainty remains around optimal duration of anticoagulation. Objectives To assess VTE recurrence and bleeding, with anticoagulation or not, beyond 6 months. Patients/Methods In SELECT‐D, after 6 months of trial treatment for VTE, patients with active cancer and residual deep vein thrombosis (RDVT) or index pulmonary embolism (PE) were eligible for randomization to a further 6 months of rivaroxaban or placebo. Patients with no RDVT stopped anticoagulation. Primary outcome was VTE recurrence at 12 months. The second randomization closed prematurely because of low recruitment when 92 of the planned 300 patients were recruited. Results Ninety‐two of 136 eligible patients were randomized to rivaroxaban or placebo. The cumulative VTE recurrence after 6 months from the second randomization was 14% with placebo and 4% with rivaroxaban (hazard ratio, 0.32; 95% confidence interval [CI], 0.06‐1.58). The major and clinically relevant non‐major bleeding rates were 0% and 0% with placebo; and 5% (95% CI, 1‐18) and 4% (95% CI, 1‐17) with rivaroxaban. In an exploratory analysis, 7 (15%) of 46 placebo patients with RDVT or an index PE experienced recurrent VTE compared to none in the 35 patients in the RDVT‐negative cohort (P = .03). Conclusion The SELECT‐D trial was underpowered to detect a statistically significant reduction in recurrent VTE with extended anticoagulation. The absence of RDVT and/or index PE, defined a population at low risk of recurrence.

Direct oral anticoagulants compared to low‐molecular‐weight heparin for the treatment of cancer‐associated thrombosis: Updated systematic review and meta‐analysis of randomized controlled trials

“…After exclusion of 716 records based on information drawn from title and abstract, 39 records were selected for full‐text assessment. Of those, we identified 4 clinical trials contributing to 9 different publications, including 5 publications on specific subgroups or post hoc analysis or on outcomes during extended treatment beyond 6 months 12‐15,22‐26 . Figure 1 shows a Preferred Reporting Items for Systematic Reviews and Meta‐Analyses flow diagram, which summarizes the process of study identification and selection 27 …”

Long-Term Treatment of Cancer-Associated Thrombosis (CAT) Beyond 6 Months in the Medical Practice: USCAT, a 432-Patient Retrospective Non-Interventional Study

“…In the DALTECAN [11] and TiCAT [12] prospective cohort studies, the rates of recurrent VTE beyond 6 months were 4.3% and 1.1% respectively and the rates of major bleeding were 4.3% and 2.7% respectively, close to the 5.7% and 2.7% observed in the USCAT study. In the RCTs, rates of recurrent VTE were 2.9% in the dalteparin group and 1.4% in the edoxaban group of the HOKUSAI study [13], and 4.0% in the rivaroxaban group of the SELECT-D trial [23] while the rates of major bleeding were 1.1% in the dalteparin group and 2.4% in the edoxaban group of the HOKUSAI study [13] and 5.0% in the rivaroxaban group of the SELECT-D trial [23]. In a recently published retrospective registry of 524 CAT patients, anticoagulation was maintained in 222 patients beyond 6 months and up to 24 months in patients with advanced cancer and receiving antineoplastic treatment.…”

Current status of treatment of cancer-associated venous thromboembolism

“…In the SELECT-D:12 m trial, the cumulative VTE recurrence from 6 months through 12 months after VTE diagnosis was 14% with placebo (n = 46) and 4% with rivaroxaban (n = 46) (hazard ratio, 0.32; 95% CI, 0.06-1.58). The major and non-major CRB rates were 0 and 0% with placebo, and 5% (95% CI, 1-18) and 4% (95% CI, 1-17) with rivaroxaban [23].…”