Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer

Abstract

BACKGROUNDRecent guidelines recommend consideration of the use of oral edoxaban or riva roxaban for the treatment of venous thromboembolism in patients with cancer. However, the benefit of these oral agents is limited by the increased risk of bleed ing associated with their use. METHODSThis was a multinational, randomized, investigatorinitiated, openlabel, noninfe riority trial with blinded central outcome adjudication. We randomly assigned consecutive patients with cancer who had symptomatic or incidental acute proxi mal deepvein thrombosis or pulmonary embolism to receive oral apixaban (at a dose of 10 mg twice daily for the first 7 days, followed by 5 mg twice daily) or subcutaneous dalteparin (at a dose of 200 IU per kilogram of body weight once daily for the first month, followed by 150 IU per kilogram once daily). The treat ments were administered for 6 months. The primary outcome was objectively confirmed recurrent venous thromboembolism during the trial period. The prin cipal safety outcome was major bleeding. RESULTSRecurrent venous thromboembolism occurred in 32 of 576 patients (5.6%) in the apixaban group and in 46 of 579 patients (7.9%) in the dalteparin group (hazard ratio, 0.63; 95% confidence interval [CI], 0.37 to 1.07; P<0.001 for noninferiority). Major bleeding occurred in 22 patients (3.8%) in the apixaban group and in 23 patients (4.0%) in the dalteparin group (hazard ratio, 0.82; 95% CI, 0.40 to 1.69; P = 0.60). CONCLUSIONSOral apixaban was noninferior to subcutaneous dalteparin for the treatment of cancerassociated venous thromboembolism without an increased risk of major bleeding. (Funded by the BristolMyers Squibb-Pfizer Alliance; Caravaggio ClinicalTrials.gov number, NCT03045406.

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 …”

“…Selected studies found eligible for inclusion were the Hokusai VTE Cancer trial, SELECT‐D (Anticoagulation Therapy in Selected Cancer Patients at Risk of Recurrence of Venous Thromboembolism), ADAM VTE (Apixaban and Dalteparin in Active Malignancy Associated Venous Thromboembolism) trial, and the Caravaggio (Apixaban for the Treatment of Venous Thromboembolism in Patients With Cancer) study 12‐15 . These studies all represent RCTs, which compared DOACs with LMWHs for the treatment of VTE in patients with cancer.…”

Are Patients with Active Cancer and Those with History of Cancer Carrying the Same Risks of Recurrent VTE and Bleeding While on Anticoagulants?

“…Evidence supporting the use of direct oral anticoagulants (DOAC) have recently become available with the publication of two dedicated noninferiority trials and one large pilot study [14][15][16] demonstrating that DOAC are non-inferior to LMWH for the prevention of recurrent VTE in this specific population, but confer a higher risk of bleeding in patients with gastrointestinal and genitourinary malignancies, which provided a significant advance in the field [17,18]. In light of these results, both DOAC and LMWH are now recommended as first-line option for the treatment of CAT by all recent guidelines [19][20][21].…”

“…While in the landmark CLOT [10] and CATCH [13] studies, and more recently in the pilot (Anticoagulation Therapy in Selected Cancer Patients at Risk of Recurrence of Venous Thromboembolism) SELECT-D study [15], "active cancer" was defined according to the Haemostasis and Malignancy SSC broad definition [22], the HOKUSAI VTE Cancer trial [14] and the recently published CARAVAGGIO trial [16] allowed including patients with "Cancer diagnosed within 2 years before enrolment" (i.e., with a "history of cancer").…”

“…Interestingly, in the HOKUSAI VTE Cancer study [14], while more than 97% of patients had "active cancer" at study entry (approximatively 52% of them having metastatic disease and 71% of them receiving anticancer therapy), 233 out of 1050 (22%) randomized patients had their cancer "cured" at the time of the index VTE event. Similarly, more than 97% of patients had "active cancer" at study entry in the CARAVAGGIO trial [16]. However, the rate of cancer "cured" at the time of the index VTE event was not reported.…”