Table 2.
Key features of major trials of heparin derivatives and DOACs in ambulatory patients with cancer
| Study | Tumour type(s) | Treatment | Comparator | Treatment duration | Randomised patients | Primary efficacy outcome | Principal safety outcome |
| PROTECHT (2009)45 | Lung, GI, pancreatic, breast, ovarian, or head and neck cancers | Nadroparin 3800 IU anti-Factor Xa od | Placebo | 4 months | 1166 (779 nadroparin, 387 placebo) |
Composite of symptomatic venous or arterial thromboembolic events: 2.0% vs 3.9%; p=0.02 |
Major bleeding: 0.7% vs 0%; p=0.18 |
| SAVE-ONCO (2012)46 | Metastatic or locally advanced solid tumours | Semuloparin 20 mg od | Placebo | Intended minimum 3 months | 3212 (1608 semuloparin, 1604 placebo) |
Composite of any symptomatic DVT, any non-fatal PE and VTE-related death: 1.2% vs 3.4%; p<0.001 |
Clinically relevant bleeding: 2.8% vs 2.0%: p=NS |
| TOPIC-1 (2012)47 | Metastatic breast carcinoma | 3000 IU certoparin od | Placebo | 6 months | 353 (174 certoparin, 179 placebo) | Symptomatic or asymptomatic VTE: 4% vs 4%; p=NS |
Bleeding events: 5.2% vs 1.7%; p=0.084 |
| TOPIC-2 (2012)47 | Stage III/IV non-small-cell lung carcinoma | 3000 IU certoparin od | Placebo | 6 months | 547 (273 certoparin, 274 placebo) | Symptomatic or asymptomatic VTE: 4.5% vs 8.3%; p=NS |
Bleeding events: 13.6% vs 7.3%; p=0.024 |
| FRAGEM (2012)48 | Advanced pancreatic cancer | Weight-adjusted dalteparin | Placebo | 12 weeks | 123 (60 dalteparin, 63 placebo) | All-type VTE during the study period: 3.4% vs 23%; p=0.002 |
NR |
| CONKO-004 (2015)49 | Advanced pancreatic cancer | Enoxaparin | Placebo | 3 months | 312 (160 enoxaparin, 152 placebo) |
First event rate of symptomatic VTE within 3 months after randomisation: 1.3% vs 9.9%; p=0.01 |
Major bleeding: 3.3% vs 4.4%; p=1.0 |
| PHACS (2017)50 | All | Dalteparin 5000 IU od | Observation | 12 weeks | 98 (50 dalteparin, 48 on observation) |
All VTE: 12% vs 21%; unstratified HR 0.64; 95% CI 0.22 to 1.72 |
Clinically relevant bleeding events: 14% vs 2%; p=0.025 |
| CASSINI (2018)51 52 75 | Solid tumours or lymphoma | Rivaroxaban 10 mg od | Placebo | 6 months | 841 (420 rivaroxaban, 421 placebo) | Composite of symptomatic or asymptomatic lower extremity, proximal DVT, symptomatic upper extremity or distal DVT, symptomatic or incidental PE; and VTE-related death: 6.0% vs 8.8%; p=0.10 |
Major bleeding: 2.0% vs 1.0%; p=0.26 |
| AVERT (2018)53 | All newly diagnosed cancers except basal cell carcinoma, squamous cell carcinoma, acute leukaemia or myeloproliferative neoplasms | Apixaban 2.5 mg two times per day | Placebo | 6 months | Target enrolment 574 | Objectively documented VTE over a follow-up period of 180 days: 4.2% vs 10.2%; p<0.001 |
Major bleeding: 3.5% vs 1.8%; p<0.05 |
DOAC, direct oral anticoagulant; DVT, deep vein thrombosis; GI, gastrointestinal; IU, international units; NR, not reported; NS, not significant; od, once daily; PE, pulmonary embolism; VTE, venous thromboembolism.