Table 4.
Randomised clinical trials (RCTs) of direct-acting oral anticoagulants (DOACs) vs low-molecular weight heparins (LMWH) for the treatment of cancer-associated thrombosis (CAT)
| Study | n | DOAC regimen and duration | Primary endpoint | Recurrent VTE DOAC vs LMWH | MB DOAC vs LMWH |
CRNMB DOAC vs LMWH |
Mortality DOAC vs LMWH |
|---|---|---|---|---|---|---|---|
|
SELECT-D trial [62] Pilot study |
406 | Rivaroxaban 15 mg twice daily for 3 weeks, then 20 mg once daily vs dalteparin (CLOT regimen) for 6–12 months | Recurrent VTE at 6 months | 4% vs 11%, HR 0.43, 95% CI 0.19–0.99; p = NR | 6% vs 4%, HR 1.83, 95% CI 0.68–4.96; p = NR | 13% vs 4%, HR 3.76, 95% CI 1.63–8.69; p = NR | 25% vs 30%, p = NR |
| HOKUSAI-VTE [65] (non-inferiority) | 1046 |
LMWH for 5 days, then edoxaban 60 mg daily vs dalteparin (CLOT regimen) for 6 months, up to 12 months Doses of 30 mg daily if: • CrCl = 30–50 mL/min·1.75 m2 • Body weight < 60 kg • Concomitant potent P-glycoprotein inhibitors |
Composite of recurrent VTE or MB at 12 months 13.5% vs 12.8%; HR 0.97, 95% CI 0.7 to 1.36, p = 0.006 for non-inferiority; p = 0.87 for superiority |
7.9% vs 11.3%, HR 0.71, 95% CI 0.48–1.06; p = 0.09 | 6.9% vs 4.0%, HR 1.77, 95% CI 1.03–3.04; p = 0.04 | 14.6% vs 11.1%, HR 1.38, 95% CI 0.98–1.94; p = NR | 39.5% vs 36.6%, HR 1.12, 95% CI 0.92–1.37; p = NR |
| ADAM-VTE [66] | 300 | Apixaban 10 mg twice daily for 7 days, then 5 mg twice daily vs dalteparin (CLOT regimen) for 6 months | MB at 6 months | 0.7% vs 6.3%, HR 0.09, 95% CI 0.013–0.780; p = 0.028 | 0% vs 1.4%, (HR not estimable) | 6.2% vs 6.3%, HR 0.93, 95% CI 0.41–1.94; p = 0.88 | 16% vs 11%, HR 1.40, 95% CI 0.82–2.43; p = 0.31 |
| CARAVAGGIO [63] (non-inferiority) | 1170 | Apixaban 10 mg twice daily for 7 days, then 5 mg twice daily vs dalteparin (CLOT regimen) for 6 months | Recurrent VTE at 6 months | 5.6% vs 7.9%, HR 0.63, 95% CI 0.37–1.07; p < 0.001 for non-inferiority; p = 0.09 for superiority | 3.8% vs 4.0%, HR 0.82, 95% CI 0.40–1.69; p = 0.60 | 9.0% vs 6.0%, HR 1.42, 95% CI 0.88–2.30; p = NR | 23.4% vs 26.4%, p = NR |
| CASTA DIVA [67](non-inferiority) | 158 | Rivaroxaban 15 mg twice daily for 3 weeks, then 20 mg once daily vs dalteparin (CLOT regimen) for 3 months | Recurrent VTE at 3 months | 6.4% vs 10.1%, SHR 0.75, 95% CI 0.21–2.66 | 1.4% vs 3.7%, SHR 0.36, 95% CI 0.04–3.43 | 12.2% vs 9.8%, SHR 1.27, 95% CI 0.49–3.26 | 25.7% vs 23.8%, HR 1.05, 95% CI 0.56–1.97 |
CAT cancer-associated thrombosis, CI confidence interval, CrCl creatinine clearance, CRNMB clinically relevant non-major bleeding, HR hazard ratio, MB major bleeding, n sample size, NR not reported, p significance level, SHR subdistribution hazard ratio, VTE venous thromboembolism
CLOT regimen: subcutaneous dalteparin at a dose of 200 IU/kg of body weight once daily for 1 month, followed by dalteparin at a dose of 150 IU/kg once daily for 2-6 months. Composite bleeding endpoint (MB plus CRNMB)