Table 3.
Randomized studies of thromboprophylaxis in cancer patients with outpatient treatment
| Study | n | Type of tumour | Treatment and dosage | Primary endpoint | CAT | MB | Minor bleeding or other non-major bleeding |
|---|---|---|---|---|---|---|---|
| PROTECHT [33] | 1150 |
Lung, digestive, breast, ovarian Moderate-high CAT risk |
Nadroparin 3800U/24 h 4 months vs no thromboprophylaxis |
Thrombosis-related |
2.0% vs 3.9% (VTE + ATE) p = 0.02 |
0.7% vs 0% p = 0.18 |
7.4% vs 7.9% p = NS |
| FRAGEM [34] | 123 |
Pancreas High CAT risk |
Dalteparin 200U/kg/24 h 4 weeks followed 150U/kg//24 h 8 weeks vs no thromboprophylaxis | Thrombosis-related |
3.4% vs 23.0% p = 0.002 |
3.4% vs 3.2% p = NS |
9% vs 3% |
| CONKO-004 [35] | 312 |
Pancreas High CAT risk |
Enoxaparin 1 mg/kg/24 h, 3 months, followed 40 mg/24 h 3 months vs no thromboprophylaxis | Thrombosis-related |
1.2% vs 9.9% p = 0.001 |
4.8% vs 3.3% p = 1.0 |
NR |
| SAVE ONCO [36] | 3212 |
Lung, digestive, kidney, ovary Moderate–high CAT risk |
Semuloparin 20 mg/24 h until a change of CT regimen vs no thromboprophylaxis |
Thrombosis-related |
1.2% vs 3.4% p < 0.001 |
1.2% vs 1.2% p = NS |
Clinically relevant non-major bleeding 1.6% vs 0.9%, OR 1.86; p = NS Clinically relevant bleeding 2.8% vs 2.0%, OR 1.41; p = NS |
| PRODIGE [37] | 186 |
Glioma High CAT risk |
Dalteparin 5000 IU/24 h 6 months vs no thromboprophylaxis | Thrombosis-related |
3.0% vs 0.0% p = NS |
3.0% vs 0.0% p = NS |
NR |
| FRAGMATIC [38] | 2202 |
Lung High CAT risk |
Dalteparin 5000 IU/24 h 24 weeks vs no thromboprophylaxis |
Overall survival HR, 1.01; p = 0.814 |
5.5% vs 9.7% p = 0.001 |
1.1% vs 0.7% p = NS |
Clinically relevant non-major bleeding 4.5% vs 0.6% |
| RASTEN [39] | 390 | Small-cell lung cancer High CAT risk | Enoxaparin 1 mg/kg/24 h, 3 months, until a change of CT regimen vs no thromboprophylaxis |
Overall survival HR, 1.11; p = 0.36 |
2.7% vs 8.4% p = 0.02 |
14% vs 3% | NR |
| AVERT [40] | 574 | Any location. Khorana ≥ 2 | Apixaban 2.5 mg twice daily) for 6 months vs no thromboprophylaxis |
Thrombosis-related, mITT analysis |
4.2% vs 10.2% p < 0.001 |
mITT analysis: 3.5% vs 1.8% p = 0.046 Treatment-period analysis: 2.1% vs 1.1% p = NS |
Clinically relevant non-major bleeding 7.3% vs 5.5%, p = NR |
| CASSINI [41] | 841 | Any location. Khorana ≥ 2 | Rivaroxaban 10 mg daily for 6 months vs no hromboprophylaxis |
Thrombosis-related, ITT analysis |
ITT analysis (primary endpoint): 6.0% vs 8.8%, p = 0.10 Intervention-period analysis 2.6% vs 6.4%; HR 0.40, 95% CI 0.20–0.80 |
Intervention-period analysis 2.0% vs 1.0%, HR 1.96, 95% CI 0.59–6.49 |
Clinically relevant non-major bleeding 2.72% vs 1.98%, p = 0.53 |
| TARGET-TP [42] | 328 |
Lung and gastrointestinalcancers High CAT risk |
Enoxaparin, 40 mg,daily for 90 days (extending up to 180 days according to ongoing risk) vs no thromboprophylaxis | Thrombosis-related |
8% vs 23% p = 0.005 |
1% vs 2% p = 0.88 |
Clinically relevant non-major bleeding 16% vs 9%; HR 0.68 95% CI 0.30–1.55 |
n: sample size, CAT cancer-associated thrombosis, MB major bleeding, vs versus, CT chemotherapy, p significance level, HR hazard ratio, CI confidence interval, ITT intention to treat, mITT modified intention to treat, VTE venous thromboembolism, ATE arterial thromboembolism, NS no significant, NR not reported