Cancer Pharmacists Group Advanced Practice Seminar on November 9th Melbourne Medicine, Nursing and Health Sciences Management of Thrombosis in the Cancer Patient Marliese Alexander Pharmacy Department, Peter MacCallum Cancer Centre School of Public Health and Preventative Medicine, Monash University
Could you recognise a DVT? Management of Thrombosis in the Cancer Patient 9th November 2014 2
Could you predict a TE? Management of Thrombosis in the Cancer Patient 9th November 2014 3
Where would you look for guidance? Management of Thrombosis in the Cancer Patient 9th November 2014 4
Agenda 1. Aetiology 2. Incidence 3. Risk Factors 4. Prophylaxis 5. Treatment 6. Evidence Based Guidelines 7. Case Scenarios Management of Thrombosis in the Cancer Patient 9th November 2014 5
Aetiology Management of Thrombosis in the Cancer Patient 9th November 2014 6
Agenda 1. Aetiology 2. Incidence 3. Risk Factors 4. Prophylaxis 5. Treatment 6. Evidence Based Guidelines 7. Case Scenarios Management of Thrombosis in the Cancer Patient 9th November 2014 7
Access Economics 2008 Incidence in Australia Direct inpatient expenditure VTE 2008 - $81.2 million Total health system costs VTE 2008 - $148 million Management of Thrombosis in the Cancer Patient 9th November 2014 8
Incidence TE hospitalised patients • 10-40% incidence DVT without prophylaxis in medical and general surgical patients • 40-60% incidence DVT without prophylaxis following major orthopaedic surgery • 5-10% of all hospital deaths (cancer and non-cancer populations) • PE most common cause of in-hospital preventable death • 2-5 fold increase risk of TE for cancer patients (above baseline which is already elevated compared to non-cancer patients) • RCT high risk medical patients - LMWH, UFH, Fondaparinux Management of Thrombosis in the Cancer Patient 9th November 2014 9
Incidence TE ambulatory patients Ambulant Cancer Patients Receiving Chemotherapy 25.0% 19.2% 20.0% 15.8% 13.9% 15.0% 10.6% 11.0% 10.0% 8.2% 5.0% 1.4% 0.0% Lung Colorectal Bladder Ovarian Pancreatic Stomach Control Khorana AA, Cancer 2013;119:648-655 Management of Thrombosis in the Cancer Patient 9th November 2014 10
Incidence TE ambulatory vs. inpatient Khorana A et al. Proc ASH 2011;Abstract 674. Management of Thrombosis in the Cancer Patient 9th November 2014 11
Incidence TE ambulatory MM patients Palumbo Leukaemia 2008;22: 414-423 Management of Thrombosis in the Cancer Patient 9th November 2014 12
Incidence ambulatory Lung Cancer Cohort • Cohort of 222 patients of 12 • 83% of events occurred in month period the ambulatory care setting • 10.8% of patients had • 67% of events pulmonary radiologically confirmed TE embolism (5 fatal) • Frequently in both SCLC and NCLC • More frequently with adenocarcinoma than squamous cell carcinoma Alexander et al, Lung Cancer 84(3): 275-280 Management of Thrombosis in the Cancer Patient 9th November 2014 13
Agenda 1. Aetiology 2. Incidence 3. Risk Factors 4. Prophylaxis 5. Treatment 6. Evidence Based Guidelines 7. Case Scenarios Management of Thrombosis in the Cancer Patient 9th November 2014 14
Risk Scores 1. Khorana Blood 2008; 111(10): 4902-7 3. Lyman JCO 2013; 10;31(17):2189-204. 2. Ay Blood 2010; 116(24):5377-82 4. Pabinger Blood 2013; 19;122(12):2011-8 Khorana predictive model for chemotherapy-associated TE(1) Risk Validation Prediction Score Rate (4) Studies Site of cancer PROTECHT Very high risk (stomach, pancreas) 2 2009 (n=381) 5/15 (33%) High risk (lung, lymphoma, gynaecologic, bladder, testicular) 1 CATS 2010 Platelet count 350 x 109/L or more 1 (n=819) 16/61 (26%) Haemoglobin level less than 100 g/L or use of red cell growth factors 1 SAVE-ONCO Leukocyte count more than 11 x 109/L 1 2012 (n=1583) 15/54 (28%) BMI 35 kg/m2 or more 1 Vienna predictive model for chemotherapy-associated TE(2) Risk Validation Prediction As Khorana plus: Score Studies Rate(4) Addition of high-grade glioma to very high risk cancers 2 Addition of myeloma & kidney carcinoma to high risk cancers 1 CATS 2010 33/61 (54%) sP-selectin 53.1ng/mL 1 (n=819) D-Dimer 1.44μg/mL 1 ASCO modified Khorana score (3) Risk Validation Prediction As Khorana plus: Score Studies Rate Addition of primary brain carcinoma to very high risk cancers Addition of renal carcinoma to high risk cancers 2 NA NA 1 Management of Thrombosis in the Cancer Patient 9th November 2014 15
Patient/Disease Related Risk Factors – Lung Cohort TE (n=24) No TE (n=198) p value* No (%) No (%) Newly diagnosed 21 (88) 150 (76) 0.06 Advanced disease 21 (88) 149 (75) 0.25 Metastatic disease 17 (71) 91 (46) 0.01 Brain metastasis 10 (42) 42 (21) 0.06 Secondary malignancy 9 (38) 31 (16) 0.01 Prior history of TE 3 (13) 8 (4) 0.17 Age>65 13 (54) 122 (62) 0.57 ECOG PS >2 2 (8) 12 (6) 0.65 Charlson Index 5 18 (75) 103 (52) 0.03 ECOG PS: Eastern Cooperative Oncology Group Performance Status. Charlson Index (Charlson et al 1987). *Log-rank test. 16
Treatment Related Risk Factors – Lung Cohort Adjusted HR Adjusted HR for potential Crude HR for age and sex confounding variables* CHT 5.69 (2.18-14.81) 5.57 (2.12-14.61) 4.97 (1.95-12.71) RT 5.19 (2.04-13.21) 5.26 (2.09-13.22) 4.97 (1.87-13.23) Surgery 1.66 (0.53-5.21) 1.51 (0.45-5.15) 0.96 (0.25-3.70) Biologic 1.66 (0.53-5.21) 1.51 (0.45-5.15) 1.01 (0.27-3.78) Time-varying cox proportional hazards model for hazard ratios, HR, and 95% confidence intervals, CI, . *Adjusted for metastatic disease, brain metastasis, secondary malignancy, new diagnosis, Charlson index 5, age and sex. 17
Moore et al. JCO 2011 Cisplatin-Based Chemotherapy • 88% within 100d Retrospective analysis: Cisplatin- starting based chemo, n=932 • TE: within start to 4weeks after last dose – 18.1% • Incidence • CRC: 38.5% • Pancreatic: 36.7% • Biliary: 28% • Gastric/GE junction: 27.2% • Ovarian: 21.1% • Head and Neck: 12.8% • Lung: 11.8% Management of Thrombosis in the Cancer Patient 9th November 2014 18
Platinum-Based Chemotherapy Lung Cohort • Retrospective analysis: Platinum- based chemo in NSCLC, n=784 • TE whilst on treatment : n=63(8%) • 70% within first 2 cycles • 8% incidence cisplatin • 5% incidence carboplatin • PFS similar regardless of TE • OS shorter with TE (9.5 vs. 12.9 months) Management of Thrombosis in the Cancer Patient 9th November 2014 19 Mellema et al. Lung Cancer 2014; 86:73-77
Hurwitz et al. JCO 2012 Bevacizumab Chemotherapy • Meta-analysis individual patient data: n=6055 (10 RCT) • TE overall with and without bevacizumab: 10.9% vs. 9.8%, ns • Tumour and host factors: 2-18% • CRC: 11-14% • APC: 6-18% • NSCLC: 6-13% • Full dose anticoagulant therapy: <1% severe bleeding event Management of Thrombosis in the Cancer Patient 9th November 2014 20
Huber et al. Arch Surg . 1992;127:310-3 . PE after surgery Days post surgery Management of Thrombosis in the Cancer Patient 9th November 2014 21
RISTOS - Agnelli G et al. Ann Surg 2006;243:89-95 . TE (DVT/PE) after surgery Days post surgery Management of Thrombosis in the Cancer Patient 9th November 2014 22
Agenda 1. Aetiology 2. Incidence 3. Risk Factors 4. Prophylaxis 5. Treatment 6. Evidence Based Guidelines 7. Case Scenarios Management of Thrombosis in the Cancer Patient 9th November 2014 23
Prevention of TE: world-wide safety priority NEVER EVENTS Venous Thromboembolism Prophylaxis and Treatment in Cancer: A Consensus Statement of Major Guidelines Panels and Call to Action Alok A. Khorana, Michael B. Streiff, Dominique Farge, Mario Mandala, Philippe Debourdeau, Francis Cajfinger, Michel Marty, Anna Falanga, and Gary H. Lyman JCO 2009 Management of Thrombosis in the Cancer Patient 9th November 2014 24
Underutilisation of Thromboprophylaxis 32 countries - 358 hospitals - 68,183 patients First patient enrolled % 'high risk' medical patients August 2, 2006 receiving appropriate TP 80% 60% Cohen AT et al. Lancet 2008;371:387-94 40% 70% 64% Kakkar et al. Ann Surg 2010; 251(2):330-338 42% 20% 0% Australia Columbia Germany Management of Thrombosis in the Cancer Patient 9th November 2014 25
Underutilisation of Thromboprophylaxis • 68,183 patients; 37,356 (55% medical) • Utilisation assessed against ACCP criteria • 15,487 medical patients indicated for TP • 6,119 (40%) received ACCP recommended TP Management of Thrombosis in the Cancer Patient 9th November 2014 26
Utilisation among hospitalised cancer medical patients – a local audit Management of Thrombosis in the Cancer Patient 9th November 2014 27
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