Teaming Up to Reduce the Burden of Cancer-Associated VTE: Applying the Latest Guidelines and Evidence in Gastrointestinal and Hematologic Malignancies and Other Cancer Settings
Chair, Alok A. Khorana, MD, FACP, FASCO, has prepared useful Practice Aids pertaining to cancer-associated VTE for this CME/MOC/CPE activity titled "Teaming Up to Reduce the Burden of Cancer-Associated VTE: Applying the Latest Guidelines and Evidence in Gastrointestinal and Hematologic Malignancies and Other Cancer Settings." For the full presentation, monograph, complete CME/MOC/CPE information, and to apply for credit, please visit us at https://bit.ly/2BVLl5z. CME/MOC/CPE credit will be available until July 1, 2021.
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Teaming Up to Reduce the Burden of Cancer-Associated VTE: Applying the Latest Guidelines and Evidence in Gastrointestinal and Hematologic Malignancies and Other Cancer Settings
1. Access the activity, “Teaming Up to Reduce the Burden of Cancer-Associated VTE: Applying the Latest Guidelines and
Evidence in Gastrointestinal and Hematologic Malignancies and Other Cancer Settings,” at PeerView.com/XDU40
PRACTICE AID
Risk Stratification for Cancer-Associated VTE
PRACTICE AID
• Age
• Ethnicity
• Comorbidities
• CBC
• Tissue factor
• D-dimer
• P-selectin
• Thrombin generation potential
• Surgery
• Hospitalization
• Systemic therapy
• CVCs
• ESA/transfusions
• Primary site
• Histology
• Grade
• Initial period
Cancer-
related
Treatment-
related
Patient-
related
Biomarkers
VTE Risk Factors
VTE is the second leading cause of death in patients with cancer and a significant predictor for all-cause mortality1
2. Access the activity, “Teaming Up to Reduce the Burden of Cancer-Associated VTE: Applying the Latest Guidelines and
Evidence in Gastrointestinal and Hematologic Malignancies and Other Cancer Settings,” at PeerView.com/XDU40
PRACTICE AID
Risk Stratification for Cancer-Associated VTE
PRACTICE AID
Khorana Risk Score2
Cancer type
Stomach +2
Pancreas +2
Lung +1
Lymphoma +1
Gynecologic +1
Bladder +1
Testicular +1
Other 0
Prechemotherapy platelet count 350 x 109/L No 0 Yes +1
Hemoglobin level <10 g/dL or using RBC growth factors No 0 Yes +1
Prechemotherapy leukocyte count 11 x 109/L No 0 Yes +1
BMI 35 kg/m2 No 0 Yes +1
Result (total)
3. Access the activity, “Teaming Up to Reduce the Burden of Cancer-Associated VTE: Applying the Latest Guidelines and
Evidence in Gastrointestinal and Hematologic Malignancies and Other Cancer Settings,” at PeerView.com/XDU40
PRACTICE AID
CBC: complete blood count; CVC: central venous catheter; ESA: erythropoiesis-stimulating agent; RBC: red blood cell; VTE: venous thromboembolism.
1. Farge D et al. Lancet Oncol. 2016;17:e452-e466. 2. https://www.mdcalc.com/khorana-risk-score-venous-thromboembolism-cancer-patients. 3. Angelini D, Khorana AA. Semin Thromb Hemost. 2017;43:469-478.
Risk Stratification for Cancer-Associated VTE
PRACTICE AID
Applying Risk Assessment3
Clinical applications of VTE risk-assessment tools
Education Screening Prophylaxis Prognosis
Increased
awareness
Early
reporting of
symptoms
Identify
occult VTE
Early
treatment
of VTE
Preventing
VTE in
high-risk
patients
Cancer
progression
Mortality
4. Decision Guide for Using
Direct Oral Anticoagulants
in Cancer-Associated VTE
Access the activity, “Teaming Up to Reduce the Burden of Cancer-Associated VTE:
Applying the Latest Guidelines and Evidence in Gastrointestinal and Hematologic
Malignancies and Other Cancer Settings,” at PeerView.com/XDU40
PRACTICE AID
Clinical Practice Guidelines for Cancer-Associated VTE1-4
Recommendations for Ambulatory Patients With Cancer (No Bleeding)
ASCO
•
•
NCCN
•
•
•
ITAC
•
•
ISTH
•
Recommendations for Hospitalized Patients With Cancer Admitted for
Medical Reasons (No Bleeding)
ASCO
NCCN
ITAC
Primary thromboprophylaxis – ONLY in
High-risk patients (Khorana score 2) with apixaban, rivaroxaban, or LMWH
Patients with myeloma on thalidomide- or lenalidomide-based regimen with
aspirin or LMWH
Primary thromboprophylaxis – ONLY in
Intermediate-/high-risk patients (Khorana score 2) with apixaban or rivaroxaban
Low-risk patients with myeloma on IMiDs with aspirin
High-risk patients with myeloma on IMiDs with apixaban or LMWH or warfarin
Primary thromboprophylaxis – ONLY in
Locally advanced or metastatic pancreatic cancer treated with systemic
anticancer therapy with LMWH
Patients on systemic anticancer therapy, at intermediate-high risk of VTE
(Khorana score 2 or cancer type [eg, pancreatic]) with DOACs (apixaban
or rivaroxaban)
Primary thromboprophylaxis – ONLY in
Cancer patients with Khorana score 2 with DOACs (apixaban or rivaroxaban)
Yes
Yes
Yes
•
•
•
•
•
•
•
•
5. Decision Guide for Using
Direct Oral Anticoagulants
in Cancer-Associated VTE
Access the activity, “Teaming Up to Reduce the Burden of Cancer-Associated VTE:
Applying the Latest Guidelines and Evidence in Gastrointestinal and Hematologic
Malignancies and Other Cancer Settings,” at PeerView.com/XDU40
PRACTICE AID
Clinical Practice Guidelines for Cancer-Associated VTE1-3
(Cont’d)
ASCO
•
NCCN
•
•
•
ITAC •
Recommendations for Patients With Cancer Undergoing Major Surgery
(No Contraindications)
ASCO
•
NCCN
•
ITAC
•
Recommendations for DOAC Therapy for Acute VTE
Yes
Initial treatment with LMWH followed by edoxaban, rivaroxaban
Yes
DOACs (apixaban, edoxaban, rivaroxaban) preferred for nongastric or
nongastroesophageal cancers
LMWH (dalteparin, enoxaparin) preferred for gastric or gastroesophageal
cancers
DOACs (dabigatran) if above regimens not appropriate/available
Yes
Initial treatment with LMWH, DOAC, unfractionated heparin, or fondaparinux
followed by LMWH or DOACs
Yes
Continue 7-10 d or up to 4 wk post dismissal in high-risk patients
Yes
Continue for 4 wk post dismissal in high-risk patients
Yes
Continue 7-10 d or up to 4 wk post dismissal in high-risk patients
•
•
•
•
•
•
•
•
6. Decision Guide for Using
Direct Oral Anticoagulants
in Cancer-Associated VTE
Access the activity, “Teaming Up to Reduce the Burden of Cancer-Associated VTE:
Applying the Latest Guidelines and Evidence in Gastrointestinal and Hematologic
Malignancies and Other Cancer Settings,” at PeerView.com/XDU40
PRACTICE AID
ASCO: American Society of Clinical Oncology; DOAC: direct oral anticoagulant; IMiD: immunomodulatory drug; ISTH: International Society on Thrombosis and Haemostasis; ITAC: International Initiative on
Thrombosis and Cancer; LMWH: low-molecular-weight heparin; NCCN: National Comprehensive Cancer Network; PE: pulmonary embolism; VTE: venous thromboembolism.
1. Key NS et al. JClinOncol. 2020;38:496-520. 2. NCCN Clinical Practice Guidelines in Oncology. Cancer-Associated Venous Thromboembolic Disease. Version 2.2020. https://www.nccn.org/professionals/physician_
gls/pdf/vte.pdf. 3. Farge D et al; International Initiative on Thrombosis and Cancer (ITAC) advisory panel. LancetOncol. 2019;20:e566-e581. 4. Wang et al. JThrombHaemost. 2019;17:1772–1778.
5. Kraaijpoel N, Carrier M. Blood. 2019;133:291-298.
Treatment Algorithm for Cancer-Associated VTE5
Cancer patient with symptomatic or incidental
DVT or PE
Does the patient have
1. Drug-drug interactions with DOACS, or
2. A high risk of bleeding?
Initiate anticoagulant treatment
with DOAC
(apixaban, edoxaban, rivaroxaban)
Initiate anticoagulant treatment
with LMWH
Consider extended anticoagulant treatment beyond 6 months if the cancer
is still active
No Yes
7. PRACTICE AID
Direct Oral Anticoagulants for
Cancer-Associated VTE
PRACTICE AID
Access the activity, “Teaming Up to Reduce the Burden of Cancer-Associated VTE: Applying the Latest Guidelines and
Evidence in Gastrointestinal and Hematologic Malignancies and Other Cancer Settings,” at PeerView.com/XDU40
FDA-Approved DOACs Available in the United States
Apixaban
Rivaroxaban
Edoxaban
Betrixaban
X
VIIIa
Dabigatran
Va
Prothrombin
Fibrinogen Fibrin
Thrombin
Xa
8. PRACTICE AID
a
In combination with aspirin.
Afib: atrial fibrillation; CAD: coronary artery disease; CV: cardiovascular; DOAC: direct oral anticoagulant; PAD: peripheral artery disease; VTE: venous thromboembolism.
1. https://natfonline.org/wp-content/uploads/2020/05/NATF-ACC-Patients-May-2020-.pdf. 2. Eliquis (apixaban) Prescribing Information. https://packageinserts.bms.com/pi/pi_eliquis.pdf. 3. Bevyxxa (betrixaban) Prescribing Information. https://bevyxxa.com/wp-content/
uploads/2020/04/BevyxxaPI.pdf. 4. Savaysa (edoxaban) Prescribing Information. https://dsi.com/prescribing-information-portlet/getPIContent?productName=Savaysa&inline=true. 5. Pradaxa (dabigatran etexilate mesylate) Prescribing Information. https://docs.boehringer-
ingelheim.com/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf. 6. Xarelto (rivaroxaban) Prescribing Information. http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/XARELTO-pi.pdf.
Direct Oral Anticoagulants for
Cancer-Associated VTE
PRACTICE AID
Access the activity, “Teaming Up to Reduce the Burden of Cancer-Associated VTE: Applying the Latest Guidelines and
Evidence in Gastrointestinal and Hematologic Malignancies and Other Cancer Settings,” at PeerView.com/XDU40
Apixaban1,2
2.5-mg and 5-mg tablets
Initial US Approval: 2012
Indication
• Stroke prevention in nonvalvular Afib
• VTE treatment
• VTE prevention in patients already treated for a blood clot
• VTE prevention after hip and knee replacement surgery
Adverse Events
• Increased risk of thrombotic events after premature discontinuation
• Risk of bleeding
• Spinal/epidural anesthesia or puncture
Betrixaban1,3
40-mg or 80-mg capsule
Initial US Approval: 2017
Indication
• VTE prevention in hospitalized acute medically ill patients
Adverse Events
• Risk of bleeding
• Spinal/epidural anesthesia or puncture
Dabigatran1,5
75-mg, 110-mg,or 150-mg capsule
Initial US Approval: 2010
Indication
• Stroke prevention in nonvalvular Afib
• VTE treatment
• VTE prevention in patients already treated for a blood clot
• VTE prevention after hip replacement surgery
Adverse Events
• Increased risk of thrombotic events after premature
discontinuation
• Risk of bleeding
• Spinal/epidural anesthesia or puncture
• Thromboembolic and bleeding events in patients with prosthetic
heart valves
• Increased risk of thrombosis in patients with triple-positive
antiphospholipid syndrome
Edoxaban1,4
15-mg, 30-mg, or 60-mg tablet
Initial US Approval: 2015
Indication
• Stroke prevention in nonvalvular Afib
• VTE treatment
Adverse Events
• Increased risk of stroke with discontinuation in patients with
nonvalvular Afib
• Risk of bleeding
• Spinal/epidural anesthesia or puncture
Rivaroxaban1,6
2.5-mg, 10-mg, 15-mg, or 20-mg tablet
Initial US Approval: 2011
Indication
• Stroke prevention in nonvalvular Afib
• VTE treatment
• VTE prevention in patients already treated for a blood clot
• VTE prevention after hip and knee replacement surgery
• VTE prevention during hospitalization and after discharge in
adults with acute medical illness
• Prevention of major CV events in patients with CAD and PADa
Adverse Events
• Increased risk of stroke after discontinuation in nonvalvular Afib
• Risk of bleeding
• Spinal/epidural hematoma