Introduction
Overview
Treatment of established Cancer-associated VTE within 6 months
Treatment of established Cancer-associated VTE beyond 6 months
Treatment of catheter-related VTE in patients with Cancer
Treatment of recurrent Cancer-associated VTE
Treatment of Cancer-associated VTE in special situations
Intracranial malignancy
Thrombocytopenia
Renal impairment
Obesity
Pregnancy
Comparison among different therapeutic anticoagulant agents
DOACs vs LMWH
DOACs vs VKA
LMWH vs VKA
SELECT-D [37] | Hokusai VTE-Cancer [22] | ADAM-VTE [44] | Caravaggio [14] | |
---|---|---|---|---|
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) |
Guidelines
ASCO | ITAC | |
---|---|---|
Duration | Initial treatment (typically first 5–10 days) + long-term treatment (6 months) + treatment after 6 months | Initial treatment (typically first 5–10 days) + early maintenance (6 months) + long-term treatment (6 months later) |
Treatment within 6 months | ||
1. Agents | LMWH (twice-daily preferred) or UFH or fondaparinux or DOACs is recommended when CrCl is ≥30 mL/min | LMWH (once-daily preferred) or DOACs or UFH or fondaparinux is recommended when CrCl is ≥30 mL/min |
2. Thrombolysis | Not mentioned | Only for patients without contraindications on a case-by-case basis (CDT considered) |
3. IVCF | Only for patients with life-threatening VTE and absolute contraindications to anticoagulation (retrievable filter preferred) | May be considered for patients with contraindications to anticoagulation |
Treatment after 6 months | The use of LMWH or DOACs or VKA should be offered to active cancer patients with intermittent risk-benefit reassessment | The use of LMWH or DOACs or VKA should be based on individual evaluation of the benefit–risk, tolerability, drug availability, patient preference, and cancer activity |
Catheter-related VTE | Not mentioned | LMWH is recommended for a minimum of 3 months and as long as the CVC is in place |
Recurrent VTE | ||
1. Anticoagulant regimen | Switching to an alternative anticoagulant regimen or increasing the dose of LMWH may be considered | For LMWH, increase the dose by 20–25% or switch to DOACs; for DOACs, switch to LMWH; for VKA, switch to LMWH or DOACs |
2. IVCF | May be offered to patients with progression of thrombosis despite optimal anticoagulation as a last resort (retrievable filter preferred) | May be considered for patients with recurrent pulmonary embolism despite optimal anticoagulation |
Incidental VTE | Treated in the same manner as symptomatic VTE | Not mentioned |
Subsegmental PE or SPVT | Treatment should be offered on a case-by-case basis | Not mentioned |
NCCN | ASCO | |
---|---|---|
Absolute contraindications | 1. Recent/acute HIT for LMWH or UFH 2. Severe renal dysfunction (CrCl < 30 mL/min) for fondaparinux or DOACs 3. Active/clinically significant liver disease for DOACs 4. Concomitant use of strong dual inhibitors/inducers of CYP3A4 and P-glycoprotein for DOACs 5. Concomitant use of inducers/inhibitors of P-glycoprotein for DOACs | 1. Active major, serious, or potentially life-threatening bleeding 2. Severe, uncontrolled malignant hypertension 3. Severe, uncompensated coagulopathy 4. Severe platelet dysfunction or inherited bleeding disorder 5. Persistent, severe thrombocytopenia (<20 × 109/L) 6. High-risk invasive procedure in a critical site 7. Concurrent use of potent P-glycoprotein or CYP3A4 inhibitors or inducers for DOACs |
Relative contraindications | 1. Severe renal dysfunction (CrCl < 30 mL/min) for LMWH 2. Past history of HIT for LMWH or UFH 3. Moderate renal insufficiency (CrCl 30–50 mL/min), weight < 50 kg, or age > 75y for fondaparinux 4. Concomitant use of inhibitors/inducers of CYP2C9, 1A2, or 3A4 for VKA 5. Urinary or gastrointestinal tract lesions for DOACs 6. Compromised renal or liver function for DOACs 7. Patients receiving nephrotoxic or hepatotoxic chemotherapy for DOACs 8. Drug-drug interactions for DOACs | 1. Intracranial or spinal lesion at high risk for bleeding 2. Active gastrointestinal ulceration at high risk of bleeding 3. Active but non–life-threatening bleeding 4. Intracranial or CNS bleeding within past 4 weeks 5. Recent high-risk surgery or bleeding event 6. Persistent thrombocytopenia (<50 × 109/L) |
ASCO | ITAC | |
---|---|---|
Intracranial Malignancy | DOACs or LMWH should be offered to patients with established VTE and primary or metastatic CNS malignancies | LMWH or DOACs should be recommended for patients with established VTE and brain tumor or cancer patients undergoing neurosurgery |
Thrombocytopenia | Anticoagulation is absolutely contraindicated when platelet count is persistently below 20 × 109/L, and relatively contraindicated when platelet count is persistently below 50 × 109/L | For established VTE, full doses of anticoagulant can be used when platelet count is>50 × 109/L and should be deliberated case-by-case when platelet count is≤50 × 109/L; prophylactic anticoagulation can be used when platelet count is>80 × 109/L |
Renal impairment | For moderate to severe renal impairment, LMWH adjusted to anti-Xa level or UFH followed by VKA are recommended | When CrCl is < 30 mL/min, UFH followed by VKA or LMWH adjusted to anti-Xa level are recommended; an external compression device can be applied |
Obesity | For obese cancer patients (BMI>40 kg/m2 or a weight>120 kg), LMWH is preferred over DOACs; the monitoring of drug-specific peak and trough levels are advised if DOACs used | A higher dose of LMWH should be offered for obese cancer patients undergoing surgery |
Pregnancy | Not mentioned | LMWH is recommended; VKA and DOACs should be avoided |