Alexander B. Pine, MD, PhD
Alfred I. Lee, MD, PhD
Injectable low–molecular-weight heparin has long been considered the standard of care for treatment of venous thromboembolism (VTE) in patients with cancer. However, low–molecular-weight heparin is costly and often disliked by patients due to injection-related discomfort and bruising. Direct-acting oral anticoagulants are an attractive option for the treatment and prevention of cancer-associated VTE, but their efficacy and safety in patients with cancer are only beginning to be defined.
Three Randomized Trials
AN INITIAL prospective observation study1 from Memorial Sloan Kettering Cancer Center suggested that the efficacy and safety of rivaroxaban (Xarelto) in the treatment of cancer-associated VTE were comparable to historical controls with low–molecular-weight heparin. Since then, three randomized controlled trials comparing the efficacy and safety of dalteparin (Fragmin) to different direct-acting oral anticoagulants in the treatment of cancer-associated VTE have been completed—the Hokusai VTE Cancer trial assessing edoxaban (Savaysa),2 the Select-D trial assessing rivaroxaban,3 and the ADAM VTE trial assessing apixaban (Eliquis).4
“Direct-acting oral anticoagulants are an attractive option for the treatment and prevention of cancer-associated VTE, but their efficacy and safety in cancer patients is only beginning to be defined.— Alexander B. Pine, MD, PhD, and Alfred I. Lee, MD, PhD
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The Hokusai VTE Cancer and Select-D studies were published earlier this year and showed decreased rates of recurrent cancer-associated VTE with edoxaban or rivaroxaban compared to dalteparin, at the expense of an increased incidence of bleeding. Preliminary results from the ADAM VTE trial were reported at the 2018 American Society of Hematology (ASH) Meeting & Exposition in December. For the primary outcome of major bleeding, no episodes occurred in 145 patients treated with apixaban and 2 episodes occurred in 142 patients treated with dalteparin; event rates were too low to assess a difference in safety or efficacy, but the study results are encouraging for the use of apixaban in the cancer VTE population.
Guideline Revisions, Regulatory Approval, and Further Studies
BASED ON the results from Hokusai VTE-Cancer and Select-D trials, the National Comprehensive Cancer Network® (NCCN®) and the International Society on Thrombosis and Haemostasis have adapted their guidelines on cancer-associated VTE with statements on the judicious use of direct-acting oral anticoagulants in cancer-associated VTE.5,6 Guidelines from both bodies caution about the use of direct-acting oral anticoagulants in patients with cancer-associated VTE who have gastrointestinal or genitourinary lesions or instrumentation due to increased rates of bleeding.
At the same time, the recent U.S. Food and Drug Administration approval of andexanet alfa (Andexxa), a recombinant factor Xa decoy molecule designed as an antidote for bleeding due to Xa inhibitors, is expected to increase utilization of direct-acting oral anticoagulants in the oncology community. Finally, two recent randomized trials exploring the efficacy and safety of thromboprophylaxis with apixaban (AVERT7) and rivaroxaban (CASSINI8) in ambulatory patients with active cancers revealed lower cancer-associated VTE rates in comparison with placebo.
IN AN EFFORT to evaluate how these new data and guidelines inform clinical practice regarding the utilization of direct-acting oral anticoagulants in cancer-associated VTE, we created a survey to probe practice patterns and guideline implementation as well as to gather data on barriers to using direct-acting oral anticoagulants to treat cancer-associated VTE. We developed the survey in collaboration with Jean M. Connors, MD, of Brigham and Women’s Hospital/Dana Farber Cancer Institute, Boston; Andrew D. Leavitt, MD, of the University of California, San Francisco; Michael B. Streiff, MD, of Sidney Kimmel Comprehensive Cancer Center, at Johns Hopkins School of Medicine, Baltimore; and Gerald A. Soff, MD, of Memorial Sloan Kettering Cancer Center, New York; with advice and assistance from Syed A. Abutalib, MD, of Cancer Treatment Centers of America, Zion, Illinois.
Readers of The ASCO Post are invited to participate in this research by completing the survey, entitled: “Perspectives and Practices in Utilization of Direct Oral Anticoagulants in Patients With Cancer-Associated Venous Thromboembolism.” The survey takes approximately 3 to 4 minutes to complete and can be taken on a mobile device or a computer. The survey link is https://yalesurvey.ca1.qualtrics.com/jfe/form/SV_3l0HxrreWZhVtBz.
Results of the survey will be reported at a later time. ■
Dr. Pine is a hematology/oncology fellow and Dr. Lee is Associate Professor of Medicine (Hematology) at Yale School of Medicine, New Haven, Connecticut.
DISCLOSURE: Drs. Pine and Lee reported no conflicts of interest.
1. Mantha S, Let al: Safe and effective use of rivaroxaban for treatment of cancer-associated venous thromboembolic disease. J Thromb Thrombolysis 43:166-171, 2017.
2. Raskob GE, et al: Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 378:615-624, 2018.
3. Young AM, et al: Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism. J Clin Oncol 36:2017-2023, 2018.
4. McBane RD, et al: Apixaban, dalteparin, in active cancer associated venous thromboembolism, the ADAM VTE trial. 2018 ASH Annual Meeting & Exposition. Abstract 421. Presented December 2, 2018.
5. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Cancer-Associated Venous Thromboembolic Disease, version 2.2018. Available at www. nccn.org/professionals/physician_gls/pdf/vte.pdf. Accessed December 12, 2018.
6. Khorana AA, et al: Role of direct oral anticoagulants in the treatment of cancer-associated venous thromboembolism. J Thromb Haemost 16:1891-1894, 2018.
7. Carrier M, et al: Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med. December 4, 2018 (early release online).
8. Khorana AA, et al: Rivaroxaban thromboprophylaxis in high-risk ambulatory cancer patients receiving systemic therapy. 2018 ASH Annual Meeting & Exposition. Abstract LBA-1. Presented December 4, 2018.