ASCO Updates Guideline on Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer

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Results from a series of randomized, controlled trials have prompted an update to the ASCO guideline on venous thromboembolism (VTE) prophylaxis and treatment in patients with cancer. The revised guideline, which had last been updated in 2019, is available from the Journal of Clinical Oncology.1

Changes to the guideline relate to two clinical scenarios—extended prophylaxis after cancer surgery and treatment of VTE. For patients with cancer undergoing surgery for malignant disease, the two oral direct factor Xa inhibitors, rivaroxaban and apixaban, are now recommended for extended thromboprophylaxis after surgery, although this is considered a weak recommendation based on the strength of the evidence.

The addition of these two oral anticoagulants as options for extended prophylaxis “may be regarded as a significant reduction of treatment burden on patients [compared with] parenteral low–molecular-weight heparin,” noted Nigel Key, MB, ChB, of the University of North Carolina at Chapel Hill. Dr. Key added that an oral regimen may be associated with better adherence to therapy.

Nigel Key, MB, ChB

Nigel Key, MB, ChB

Anna Falanga, MD

Anna Falanga, MD

The second major revision to the guideline involves the addition of apixaban as an option for patients requiring treatment for VTE; this is a strong recommendation based on high-quality evidence. Dr. Key commented that apixaban is commonly used in non–cancer-associated thrombosis and that “it was appropriate to update the guideline according to recent evidence reporting that it’s a perfectly good option in cancer-associated thrombosis.”

Anna Falanga, MD, of the University of Milan Bicocca, commented that the availability of multiple choices for cancer-associated thrombosis treatment, including different oral direct anti-Xa anticoagulants, low–molecula- weight heparin (LMWH), or vitamin K antagonists, is relevant, as “it allows physicians to tailor the best VTE treatment according to the cancer type, the patient characteristics, preexisting conditions and comedications, and, very importantly, the patient[‘s] preference.”

Evidence Supporting Updates

Two randomized, controlled trials evaluated the direct factor Xa inhibitors rivaroxaban and apixaban for extended thromboprophylaxis after surgery in patients with cancer:

The PROLAPS-II trial compared rivaroxaban against placebo in 582 patients undergoing laparoscopic surgery for colorectal cancer.2 The composite endpoint of symptomatic VTE, asymptomatic deep vein thrombosis (DVT), or VTE-related death in the first 28 days after surgery was significantly less frequent with rivaroxaban than with placebo (1.0% vs 3.9%; P = .03).

A randomized, open-label trial compared oral apixaban vs subcutaneous enoxaparin as postoperative thromboprophylaxis in 400 patients undergoing surgery for suspected or confirmed gynecologic cancer.3 Apixaban and enoxaparin were associated with similar rates of major bleeding, clinically relevant nonmajor bleeding, and VTE. Adherence rates did not differ between groups, but patients receiving apixaban reported increased ease and decreased pain while taking the medication.

Three randomized, controlled trials assessed apixaban as VTE treatment in different cancer settings:

  • The open-label noninferiority CARAVAGGIO trial compared oral apixaban against subcutaneous dalteparin in 1,170 patients with cancer and symptomatic or incidental acute proximal DVT or pulmonary embolism.4 Rates of recurrent VTE with apixaban and dalteparin were 5.6% and 7.9%, respectively (P < .001 for noninferiority), and major bleeding rates were 3.8% and 4.0% (P = .60).
  • The open-label superiority ADAM VTE trial compared apixaban and dalteparin in 287 patients with cancer-associated VTE.5 Major bleeding rates were 0% and 1.4%, respectively, and recurrent VTE rates were 0.7% and 6.3%, respectively.
  • A smaller trial compared apixaban and weight-adjusted subcutaneous LMWH in 138 patients with cancer and acute DVT. Among 100 patients with active malignancy included in the analysis, there was no difference between apixaban and LMWH in major bleeding rates, recurrent DVT or VTE rates, or minor bleeding rates.6

Next Steps

The guideline co-chairs noted there is more work to be done related to both new recommendations. According to Dr. Key, “more studies are needed to strengthen the evidence for oral direct factor Xa inhibitors as extended prophylaxis after surgery.”

In addition, because the trials were conducted specifically in patients with colorectal and gynecologic cancers, the generalizability of the results is unclear. The role of these agents in patients undergoing surgery for primary brain tumors needs further evaluation, Dr. Key noted, adding those patients “seem to be a different group in terms of potential thrombosis and bleeding risks.”

Regarding VTE treatment, Dr. Key said that bleeding remains a risk with all current agents. Anticoagulants that inhibit factor XI or XIa could potentially have a lower risk of bleeding, he commented, but are likely a few years away. There also remains a question about the optimal duration of therapy. Dr. Key explained there are “still open-ended questions in terms of anticoagulant therapy beyond 6 months in many of these patients [in terms of] risk vs benefit.”

Dr. Falanga added that prevention and treatment of arterial thrombosis in patients with cancer is another area of unmet need. “We do not know if the current approaches to prophylaxis of arterial thrombosis are equally effective in the oncologic compared to the nononcologic patient,” she said, “just as we do not know if the therapy of arterial thrombosis should be modified or readapted in the oncological patient.”

Finally, Dr. Falanga noted there is uncertainty regarding the optimal use of antithrombotic drugs in specific patient populations, such as in those with moderate or severe thrombocytopenia. 


1. Key NS et al: Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO guideline update. J Clin Oncol. April 19, 2023 (early release online).

2. Becattini C et al: Rivaroxaban vs placebo for extended antithrombotic prophylaxis after laparoscopic surgery for colorectal cancer. Blood 140:900-908, 2022.

3. Guntupalli SR et al: Safety and efficacy of apixaban vs enoxaparin for preventing postoperative venous thromboembolism in women undergoing surgery for gynecologic malignant neoplasm. JAMA Netw Open 3:e207410, 2020.

4. Agnelli G et al: Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med 382:1599-1607, 2020.

5. McBane RD II et al: Apixaban and dalteparin in active malignancy-associated venous thromboembolism. J Thromb Haemost 18:411-421, 2020.

6. Mokadem ME et al: Efficacy and safety of apixaban in patients with active malignancy and acute deep venous thrombosis. Vascular 29:745-750, 2021.

Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, June 2, 2023. All rights reserved.