Table 1 Comparison among different randomized clinical trials assessing the efficacy and safety of DOACs in the treatment of cancer-associated VTE

Trial design

Open-label, pilot

Open-label, noninferiority

Open-label, investigator-initiated

Open-label, controlled, investigator-initiated, noninferiority

Number of patients

406

942

300

1155

DOACs

Rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily for 2–6 months)

Edoxaban (dalteparin for at least 5 days, followed by edoxaban 60 mg once daily, for 12 months)

Apixaban (10 mg twice daily for the first week, followed by 5 mg twice daily for 6 months)

Apixaban (10 mg twice daily for the first week, followed by 5 mg twice daily for 6 months)

Comparators

LMWH (daltaparin 200 IU/kg once daily for the first month, followed by 150 IU/kg daily for 2–6 months)

LMWH (daltaparin 200 IU/kg once daily for the first month, followed by 150 IU/kg daily for 12 months)

LMWH (daltaparin 200 IU/kg once daily for the first month, followed by 150 IU/kg daily for 6 months)

LMWH (dalteparin 200 IU/kg once daily for the first for the first month, followed by 150 IU/kg once daily for 6 months)

Inclusion criteria

Patients with active cancer and symptomatic or incidental PE, or symptomatic lower extremity proximal DVT

Patients with active cancer and acute symptomatic or incidental proximal DVT and/or PE

Patients with active cancer and acute extremity DVT, PE, splanchnic or cerebral vein thrombosis

Patients with active cancer and acute symptomatic or incidental proximal DVT or PE

Cancer types

Solid and hematologic malignancies (other than basal-cell or squamous-cell skin carcinoma)

Gastrointestinal, lung, urogenital, breast, hematological, and gynecological cancer

Solid and hematologic malignancies

Cancers other than basal-cell or squamous-cell carcinoma of the skin, primary brain tumor, intracerebral metastases, or acute leukemia

Primary outcome measurements

VTE recurrence

The composite of VTE recurrence or major bleeding

Episode of major bleeding

VTE recurrence

Primary outcome results

Rivaroxaban 4% (95% CI, 2 to 9%); Dalteparin 11% (95% CI, 7 to 16%); (HR, 0.43; 95% CI, 0.19 to 0.99)

Edoxaban 19.4%; Dalteparin 15.0%; (RD, 4.4%; 95%CI, − 4.1 to 12.8%)

Apixaban 0%; Dalteparin 1.4%;(P = 0.138)

Apixaban 5.6%; Dalteparin 7.9%; (HR, 0.63; 95% CI, 0.37 to 1.07; P < 0.001 for noninferiority)