Primary _ in Ambulatory Cancer Patients ...

Taylor Butler, PharmD, BCOPDecentralized Clinical PharmacistDepartment of Veteran AffairsTennessee Valley Healthcare System
Primary Thromboprophylaxis inAmbulatory Cancer Patients:Current Guidelines and Updated Evidence
Presentation Objectives
Review and contrast theAmerican Society of Clinical Oncologist (ASCO), European Society of Medical Oncologist (ESMO), and National Comprehensive Cancer Network (NCCN) guidelines for venous thromboembolism (VTE) prophylaxis in the ambulatory settingDiscuss the current evidence of VTE prophylaxis in the ambulatory setting
Why is VTE important in cancer?
VTE risk in the ambulatory setting is 8-19% in cancer, depending on the cancer type, while a matched cohort without cancer was only 1.4%In pancreatic cancer, symptomatic VTE was significant for a worse response rate, progression-free survival, and overall survival
Source: 1 Khorana AA, Dalal M, Lin J, et al. Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States. Cancer 2013; 119: 648-55.2 Mandala M, Reni M, Cascinu S, et al. Venous thromboembolism predicts poor prognosis in irresectable pancreatic cancer patients. Ann Oncol 2007; 18: 1660-5.
ASCO Guidelines
Routine thromboprophylaxis not recommended (Strength of recommendation: evidence-based, strong)Consider with “highly select high-risk patients” (evidence-based, weak)Multiple myeloma patients with antiangiogenesis therapy should receive prophylaxis with LMWH or low-dose aspirin based on risk (evidence-based, strong)
Source: Lyman GH, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guidelines update. J Clin Oncol 2013; 31(17): 2189-205.
ASCO Guidelines
Other pertinent recommendationsAssess patients periodically for VTE risk (informal consensus, strong)Oncology professionals should educate patients about the s/sx of VTE (informal consensus, strong)
Source: Lyman GH, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guidelines update. J Clin Oncol 2013; 31(17): 2189-205.
ESMO Guidelines
Patient receiving palliative chemotherapy for locally advanced or metastatic diseaseNot recommended (Level of evidence and grade of recommendation: II,C)Consider in high risk patients (II, C)Consider aspirin, LMWH, or adjusted-dose warfarin for multiple myeloma patients receiving thalidomide plus dexamethasone or chemotherapy (II, B)Patient receiving adjuvant chemotherapy and/or hormone therapy (including with central venous catheters)Not recommended (I, A)
Source: Mandala M, Falanga A, and Rolia F. Management of venous thromboembolism (VTE) in cancer patients: ESMO clinical practice guidelines. Ann Oncol 2011; 22(Suppl 6): vi85-92.
NCCN Guidelines
Ambulatory patients with cancerNo routinepxrecommended outside clinical trial (category 2A)Multiple Myeloma receiving immunomodulators (IMiDs)High risk: Recommend anticoagulant VTE prophylaxis (category 2A)Low risk: Recommend aspirin(category 2A)Provider/patient discussion
Source: National Comprehensive Cancer Network. Cancer-associated venous thromboembolic disease. Version 1.2016. Updated 7/22/2016.
Khorana Predictive Model
Site of primary cancerVery High Risk (2 points) – stomach, pancreasHigh Risk (1 pt) – lung, lymphoma, gynecologic, genitourinary except prostatePretreatment platelet count ≥ 350x 109/L(1 pt)Hgb < 10 g/dL or use of erythropoietin-stimulating agents (1 pt)Pretreatment leukocyte count > 11 x 109/L (1 pt)BMI ≥ 35 kg/m2(1 pt)
Source: Khorana AA, KudererNM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111(10): 4902-7.
Khorana Predictive Model
Multiple Myeloma Risk Factors
Multiple Myeloma Risk Assessment
Low0-1 risk factorsAspirin 81-325 mg once dailyHigh≥ 2 individual/myeloma risk factorsProphylactic dose enoxaparin or full-dose warfarin (target INR = 2-3)
Source: Palumbo A, Rajkumar SV, Dimopoulos MA, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia 2008; 22: 414-23.
Overview of Guidelines
Literature Review
Review parameters from January 2015 – May 2017PubMedASCO, MASCC, and ESMO abstractsLustig DB, Rodriguez R, and Wells PS. Implementation and validation of a risk stratification method at The Ottawa Hospital to guide thromboprophylaxis in ambulatory cancer patients at intermediate-high risk for venous thrombosis. Thromb Res 2015; 136(6): 1099-102.Cella CA, Di Minno G, Carlomagno C, et al. Preventing venousthromboembolism in ambulatorycancerpatients: The ONKOTEV study. Oncologist 2017; 22(5): 601-8.
Meta-analysis – Pancreatic Cancer (2016)
Tun NM, Guevara E, and Oo THN = 738 ambulatory advanced pancreatic cancer patientsVTE incidence was 2.1% with LMWH versus 11.2% in the control group (P<0.0001)Bleeding risk was non-significantly higher
Source:Tun NM, Guevara E, and Oo TH. Benefit and risk of primary thromboprophylaxis in ambulatory patients with advanced pancreatic cancer receiving chemotherapy: a systematic review and meta-analysis of randomized controlled trials. Blood Coagul Fibrinolysis 2016; 27(3): 270-4.
Meta-analysis – Lung Cancer (2017)
Fuentes HE, Oramas DM, Paz LH, et al.N = 5107 with lung cancerTreatment groups included LMWH, UFH, and warfarin50% decrease in VTE with LMWHNo increased risk of bleedingMortality benefit when ALL VTE prevention modalities were combinedHigher bleeding incidence when all VTE modalities were combined
Source:Fuentes HE, Oramas DM, Paz LH, et al. Meta-analysis on anticoagulation and prevention of thrombosis and mortality among patients with lung cancer. Thromb Res 2017; 154: 28-34.
New Oral Anticoagulants (NOACs)
Upcoming Trials
Conclusion
ASCO, ESMO, and NCCN guidelines have similar recommendationsregarding VTE prophylaxis in ambulatory cancer patientsGeneral consensus recommends against routine prophylaxis outside of patients diagnosed with multiple myeloma who are receiving antiangiogeneic agentsPeriodic risk assessments and patient discussions are vital in the decision-making processNew evidence is needed, including a validated risk assessment adopted into clinical practice