Cancer Associated Thrombosis: An Update BATH...Cancer Associated Thrombosis: An Update Disclosures...
Transcript of Cancer Associated Thrombosis: An Update BATH...Cancer Associated Thrombosis: An Update Disclosures...
Professor Anthony MaraveyasHull University Teaching Hospitals NHS Trust&Hull-York Medical School.
Cancer Associated Thrombosis: An Update
Disclosures
• Honoraria: Bristol-Myers Squibb (BMS), Bayer, Daiichi Sankyo• Advisory Boards: BMS, Bayer Leo • Speaker's Bureau: Bayer, Pfizer • Grant: BMS, Leo
The History of Cancer and Thrombosis
1. Trousseau A. Clin Med Hotel Dieu Paris 1865;3:654–712.2. Bouillaud JB & Bouillaud S. Arch Gen Med 1823;1:188–204;3. Billroth T. Lectures on surgical pathology and therapeutics: a
handbook for students and practitioners, 1878;2:1829–1894.
Close interrelation between cancer and thrombosis:‘two-way’ (clinical) association
• Thrombosis can occur as a complication of cancer1
• Thrombosis can be the first presenting sign of occult cancer2
• Presence of cancer cells in thrombotic material3
Virchow’s Triad in Cancer Associated Thrombosis
Virchow’s Triad in cancer2
HYPERCOAGULABILTY
Increased blood cell activation and aggregability, e.g., NETs ‘tumour educated’ platelets
Loss of haemostasis with increase in pro-coagulants, eg, increased fibrinogen, TF +MVs.
VASCULAR DAMAGE
Damaged or dysfunctional endothelium Loss of anticoagulant nature and
therefore acquisition of a procoagulantnature
Endothelial layer permeability / Angiogenesis
CIRCULATORY STASIS
Increased vascular compression/distortion Increased stasis due to immobility (being bed-bound, in
a wheelchair).
Adapted from Blann AD and Dunmore S Cardiology Research and Practice Volume 2011
Possible mechanisms in cancer patients
cfDNA, cell-free DNA; FXIIa, activated factor XII; NETs, neutrophil extracellular traps; P-sel, P-selectin; TF+ MVs, tissue factor-positive microvesicles; TF, tissue factor; vWF, von Willebrand factor. Adapted from Hisada Y et al. J Thromb Haemost 2015;13:1372–1382.
MonocytePlatelet EndotheliumcfDNA
vWF P-sel
TF+ MVs Neutrophil
ChemotherapyTumour
Venous thrombus
FXIIaNETs
TF NETs
VTE in Patients with Cancer – Cancer-Associated ThrombosisRisk factors:1
Patient-related Tumour-related Treatment-related Biomarkers
Prevalence and risk ratios: Approximately 20% of first venous thromboembolic
events occur in patients with active cancer2
VTE is a common cause of death in patients with cancer3–5
VTE recurrence rate is twice as high in patients with VTE and cancer compared with those with VTE and no cancer2,6,7
Common cancers contribute the greatest burden2
6
A
1. Ay C et al, Thromb Haemost 2017;117:219–230; 2. Cohen AT et al, Thromb Haemost 2017;117:57–65; 3. Horsted F et al, PLoS Med 2012;9:e1001275; 4. Khorana AA et al, J Thromb Haemost 2007;5:632–634; 5. Chew HK et al, Arch Intern Med 2006;166:458–464; 6. Sallah S et al, Thromb Haemost 2002;87:575–579; 7. Stein PD et al, Am J Med 2006;119:60–68
Incidence and Prevalence of VTE After Cancer Diagnosis
Incidence rate of first VTE Prevalence of first VTECommon cancer types (%) First VTE (N=6592)
Prostate (men) 17.5
Breast (women) 15.1
Lung 13.9
Colon 12.5
Haematological 10.1
Ovarian (women) 9.5
Bladder 4.8
Uterus (women) 4.2
Pancreas 3.9
Stomach 3.6
Brain 2.5
0 5 10 15
Bladder
Breast
Prostate
Haematological
Colon
Uterus
Lung
Stomach
Ovary
Brain
Pancreas
Incidence rate of first VTE per 100 patient-years
Cohen AT et al, Thromb Haemost 2017;117:57–65
How does the patient present?
‘Unprovoked’ VTE • 4% end up having an underlying cancer diagnosis within 12 months of presentation
Hospital acquired • The most lethal
– Frailty– Coexisting complications– First and last port of call (advanced presentation with complications)– Procedures (surgery) – Immobility (Bone metastases-Brain metastases)– Bleeding risks (not allowing thromboprophylaxis)– Difficult to diagnose from what else is going on
Ambulant • Conventional presentation • Incidental
Silver In: The Hematologist - modified from Blom et. al. JAMA 2005;293:715
• Population-based case-control (MEGA) study
• N=3220 consecutive patients with 1st VTE vs. n=2131 control subjects
• CA patients = 7x OR for VTE vs. non-CA patients
Effect of Malignancy on Risk of Venous Thromboembolism (VTE)
0
10
20
30
40
50
Hem
atol
ogic
al
Lung
Gas
troi
ntes
tinal
Bre
ast
Dis
tant
met
asta
ses
0 to
3 m
onth
s
3 to
12
mon
ths
1 to
3 y
ears
5 to
10
year
s
> 15
yea
rs
Adj
uste
d od
ds ra
tio
Type of cancer Time since cancer diagnosis
2822.2 20.3
4.9
19.8
53.5
14.3
2.6 1.13.6
Dia
gnos
is
Star
t che
mo
+ in
patie
nt
Che
mo
Rel
apse
Met
asta
sis
Remission
Ris
k of
ven
ous
thro
mbo
embo
lism
Cancer journey
General population
Cancer patient
The Cancer Journey and VTE Risk
Figure adapted from .Lyman GH et al. Cancer 2011;117:1334–1349
LMWH Vs Warfarin
Treatment of Cancer Associated Thrombosis
Warfarin failure in Cancer Patients
20
0 1 2 3 4 5 6 7 8 9 10 11 12Time (months)
30
0
10
Cum
ulat
ive
prop
ortio
n re
curre
nt V
TE (%
)
Cancer
No cancer
20.7% vs 6.8%; HR 3.2 at 1 year
Warfarin to maintain INR 2–3
Major bleeding 12.4% vs 4.9%; HR 2.2
VTE and bleeding not predicted by INR
Number of
patients
Cancer 181 160 129 92 73 64
No cancer 661 631 602 161 120 115
Prandoni P, et al. Blood. 2002;100:3484-3488.
Amiodarone26%
Ciprofloxacin22%Cotrimoxazole
15%
Metronidazole8%
Fluconazole7%
Omeprazole5%
Cimetidine5%
NSAID‘s3%
Erythromycin3%
Carbamazepine3%
APAP3%
Frequency of Potentially Interacting Drugs
n=59
Capecitabine
Tamoxifen
Sorafenib
Sunitinib
Twilley C. H. 2002
5 to 7 days
Dalteparin 200 IU/kg OD
Vitamin K antagonist (INR 2.0 to 3.0) x 6 mo
Control Group
Dalteparin 200 IU/kg OD x 1 mo then ~150 IU/kg OD x 5 mo
Experimental Group
1 month 6 monthsLee AY, et al. N Engl J Med. 2003;349:146-153.
Cancer patients with acute DVT or PE (n=677)
CLOT Study: Reduction in Recurrent VTE
CLOT Study: Reduction in Recurrent VTE
Lee et.al. N Engl J Med, 2003;349:146
0
5
10
15
20
25
Days Post Randomization0 30 60 90 120 150 180 210
Prob
abilit
y of
Rec
urre
nt V
TE, % Risk reduction = 52%
p-value = 0.0017
Dalteparin
OAC
Recurrent VTE
Study RR (95% CI)*,1 RR (95% CI)*,1 ARR
CLOT2 0.51 (0.33–0.79) 7.8%
Hull3 0.44 (0.19–0.99) 9.0%
Deitcher4 0.66 (0.18–2.52) 3.4%
Romera5 0.26 (0.06–1.02) 15.7%
CATCH6 0.69 (0.45–1.07) 3.1%
Efficacy and Safety Profile of LMWH Versus VKAs in the Treatment of CAT
Recurrent VTE
LMWH is associated with a significant reduction in the risk of recurrent VTE without a significant increase in major bleeding events versus VKA
0.01 0.1 0.2 0.5 1 2 3
Favours LMWH Favours VKA
0.1 0.2 0.5 1 2 5 10 100
Favours LMWH Favours VKA
*Random effects model
1. Carrier M, Prandoni P, Expert Rev Hematol 2017;10:15–22; 2. Lee AYY et al, N Engl J Med 2003;349:146–153; 3. Hull RD et al, Am J Med 2006;119:1062–1072; 4. Deitcher SR et al, Clin Appl Thromb Hemost 2006;12:389–396; 5. Romera A et al, Eur J Vasc Endovasc Surg 2009;37:349–356; 6. Lee AYY et al, JAMA 2015;314:677–686
Study RR (95% CI)*,1 RR (95% CI)*,1 ARI
CLOT2 1.57 (0.79–3.14) 2.0%
Hull3 1.00 (0.38–2.64) 2.1%
Deitcher4 3.04 (0.52–18.99) 6.1%
CATCH6 1.09 (0.51–2.32) 0.3%
Major bleeding events
CAT, cancer-associated thrombosis; CI, confidence interval; HR, hazard ratio; LMWH, low molecular weight heparin; VKA, vitamin K antagonist; VTE, venous thromboembolism*Dalteparin versus VKA; in the VKA arm the estimated time in therapeutic range was 46% (30% below and 24% above); #tinzaparin versus warfarin; in the warfarin arm the time in therapeutic range was 47% (26% below and 27% above); ‡meta-analysis included four other small studies in addition to the CLOT study; §meta-analysis included three other small studies in addition to the CLOT study 1. Lee AYY et al, New Engl J Med 2003;349:146–153; 2. Lee AYY et al, JAMA 2015;314:677–686; 3. Akl EA et al, Cochrane Database Rev 2014;7:CD006650
LMWH: Effective and Safe – Residual Burden of Disease
LMWH monotherapy LMWH overlapping with VKA
HR (95% CI)
n/N (%) n/N (%)
Recurrent VTE
CLOT study*1 27/336 8.0 53/336 15.8
CATCH study#2 31/449 6.9 45/451 10.0
Meta-analysis‡3 42/591 7.1 82/571 14.4
Major bleeding
CLOT study*1 19/338 5.6 12/335 3.6
CATCH study#2 12/449 2.9 11/451 2.4
Meta-analysis§3 37/556 6.7 32/536 6.0
0.1 1 10Favours LMWH Favours VKA
Not reported
Multivariate predictors of VTE recurrence
Population-based cohort study performed using the Olmstead county database; 477 patients (1533 patient-years of follow-up) with cancer and VTE were identified
Chee CE et al, Blood 2014;123:3972‒3978
Risk of VTE Recurrence May Depend on Tumour Type, Stage of Disease and Co-morbidities
70
Cum
ulat
ive
inci
denc
e of
VTE
re
curr
ence
(%)
1009080
605040302010
00 1 2 3 4 5 6 7 8 9 10
Time after incident VTE (years)
Active cancer without predictors Active cancer with predictors Other secondary VTE
Characteristic HR 95% CI p-value
Stage IV pancreatic cancer 6.38 2.69–15.13 <0.0001
Brain cancer 4.57 2.07–10.09 0.0002
Myeloproliferative or myelodysplastic disorder 3.49 1.59–7.68 0.002
Ovarian cancer 3.22 1.57–6.59 0.001
Stage IV cancer (non-pancreas) 2.85 1.74–4.67 <0.0001
Lung cancer 2.73 1.63–4.55 0.0001
Neurological disease with leg paresis 2.38 1.14–4.97 0.02
Cancer stage progression 2.14 1.30–3.52 0.003
Warfarin therapy 0.43 0.28–0.66 <0.0001
Cumulative incidence of first VTE recurrence
CI, confidence interval; HR, hazard ratio; LMWH, low molecular weight heparin; VTE, venous thromboembolism
Duration of Anticoagulation After VTE in Real-World Clinical Practice: RIETE Registry (N=6944)
Fewer than 50% of patients with cancer are treated for >12 months
Ageno W et al, Thromb Res 2015;135:666–672
Cum
ulat
ive
inci
denc
e (%
)
Days
28%9%
Unprovoked
Persistence in patients with CAT(after excluding patients who died): only 43.2% at 1 year still receiving anticoagulant treatment
TransientCancer
Persistence with Index Therapy in Patients with Cancer Is Higher With Warfarin Than LMWH
*Discontinuation was defined as a gap of no more than 60 days between the end of the days of supply of a dispensing and the start date of the next dispensing of the index therapy, if any
Khorana AA et al, Res Pract Thromb Haemost 2017;1:14–22
Cohort Median treatment duration
Kaplan–Meier rates6 months 12 months
LMWH 3.3 37% 21%
Warfarin 7.9 61% 35%
Warfarin (n=1403)
LMWH (n=735)
100
75
50
25
0
Prop
ortio
n of
pat
ient
s st
ill o
n in
dex
ther
apy
(%)
0 2 4 6 8 10 12Time (months)
FOR REACTIVE USE ONLY.
Adjusted OR (95% CI)Pancreatic
Stomach
Ovarian
Brain
Lung
Age ≥80 vs 60–69 years
Radiation therapy vs chemotherapy
OR adjusted by age, gender, tumour type, cancer therapy, lifestyle factors and co-morbidities; prostate cancer was used as a reference group for calculating ORs by tumour location
Katholing A et al, ESMO 2016: Poster 1479P
FavoursVKA
Favours parenteral therapy
Database Analysis: Predictive Factors for Use of Parenteral Versus OACs for VTE Treatment in Patients with Active CancerMatched cohort retrospective database analysis (2008–2015)
—Retrospective analysis of data from general practices in England from patients with cancer and VTE• 1228 parenteral anticoagulant users
were matched to 1228 VKA users—Some tumour types were strongly
associated with preferential use of parenteral therapies
0.25 1 4 16
CI, confidence interval; LMWH, low molecular weight heparin; OAC, oral anticoagulant; OR, odds ratio; VKA, vitamin K antagonist; VTE, venous thromboembolism
Long Term Treatment of VTE in Cancer
ASCO: Extended anticoagulation with LMWH or VKA may be considered beyond 6/12 for patients with metastatic disease or patients who are receiving chemotherapy.• Length of secondary prophylaxis?
– LONGHEVA NCT01164046 (Netherlands) – Warfarin vs LMWH (+6 m)
– ALICAT ISRCTN37913976 (UK)- LMWH vs No anticoagulant (+6 m)– Funded by HTA NIHR
10%
4% 5% 4%
Month 1-12N=334
Month 1N=334
Month2-61N=302
Month 7-12N=192
Incidence of Major Bleeding Events
1.9% per month through the whole study (12 months)
• Incidence of new or recurrent VTE: 11.1% (1.4% per patient-month)
• 154 (46.1%) patients died, 115 during the study period (4/115 due to
VTE, 2/115 due to bleeding Adapted from Kakkar A, et al. J Thromb Haemost. 2013;11:AS12.3.
Cumulative Probability of Survival
Reason for Death Frequency
Underlying Cancer 105
VTE 4
Bleeding 2
Long-term Management of VTE in Cancer Patients: The DALTECAN Study
What Is Important for Patients?
1. No interference with cancer treatment 39%2. Efficacy/recurrent VTE 24%3. Major bleeding 19%4. Route of administration 13%
5. Monitoring 2%6. Minor bleeding 2%7. Frequencency of administration 1%
Noble S et al, Haematologica 2015;100:1486–1492
From LMWH to DOACS (Anti fXa inhibitors)
Treatment of Cancer Associated Thrombosis
*Rivaroxaban 15 mg BID for 21 days followed by 20 mg OD. For patients with CrCl 30–49 ml/min dosing recommendations as in rivaroxaban SmPC; #Dalteparin 200 IU/kg OD for the first 30 days followed by 150 IU/kg ODbid, twice daily; CrCl, creatinine clearance; DVT, deep vein thrombosis; od, once daily; PE, pulmonary embolism; VTE, venous thromboembolismThe second randomization phase for extended treatment of VTE from 6 to 12 months for patients with PE as an index event or patients with Residual DVT at 5 month assessment was closed due to low recruitment. Sample size reduced from 530 to 400 patients for main trial comparison (95% CI for VTE recurrence +/-4.5%)Young A et al, Thromb Res 2016;140:S172–S173; EudraCT number: 2012-005589-37; Bach M et al, Thromb Haemost 2016;116:S24–S32; Data on File
Study design: Prospective, randomized, open-label, multicentre pilot phase III study
select-d: Phase III Pilot Study Comparing Rivaroxaban versus Dalteparin for the Treatment of Cancer Associated Thrombosis
Stratification variables:• Stage of disease• Baseline platelet count • Type of VTE • Risk of clotting by tumor type
Study population: Cancer patients
with symptomatic DVT and/or PE RVT negative
before 6 months N~130 No treatment
Follo
w-u
p
R
6 months
Rivaroxaban
Placebo
R
12 months
PE index event or RVT positive
before 6 months N~300
N~530 Rivaroxaban*
Dalteparin#
DVT, deep vein thrombosis; PE, pulmonary embolism; VTE, venous thromboembolism; Ci, Confidence interval Young A et al. J Clin Oncol 2018;doi:10.1200/JCO.2018.78.8034
select-d Primary Outcome: Lower Incidence of VTE Recurrence Events with Rivaroxaban Versus Dalteparin
DalteparinRivaroxaban
Number at riskDalteparin 203 171 139 115
Rivaroxaban 203 174 149 134
40
35
30
25
20
15
10
5
00 1 2 3 4 5 6
Time from trial entry (months)
VTE
recu
rren
ce (%
)Outcome at 6 months Rivaroxaban
(n=203)Dalteparin
(n=203)VTE recurrence, % (95% CI) 4 (2–9) 11 (7–16)
Lower limb DVT/PE recurrence,% (95% CI) 3 (1-7) 9 (6-15)
Type of PE, NoSymptomaticIncidentalFatal PE
211
261
select-d Secondary Outcome: Incidence of Major, Fatal and Clinically Relevant Non-Major Bleedings
2.90.5
3.45.4
0.5
12.3
0
5
10
15
20
Major bleeding Fatal Bleeding CRNMB
Patie
nts
(%)
Dalteparin Rivaroxaban
• All bleedings events were adjudicated .Overall survival at 6 months was 75%(63-76%) in the rivaroxaban group and 70%(69-81%) in the dalteparin group.
• CRNMB, clinically relevant non-major bleeding
Young A et al. J Clin Oncol 2018;doi:10.1200/JCO.2018.78.8034
Most Major Bleedings events were Gastrointestinal Bleedings*. Most CRNMB were GI or urologicNo Central Nervous System Bleeding was observed in rivaroxaban and dalteparin groups.
Treatment for up to 12 months (at least 6 months) Efficacy and safety data collected during the entire 12 month study period Independent blind adjudication of all suspected outcomes Severity of major bleeding at presentation also adjudicated
Hokusai VTE – Cancer Study Design
Raskob GE et al, N Engl J Med 2018;378:615–624
Primary Outcome: Time to First Occurrence of Recurrent VTE or Major Bleeding
13.5%
12.8%
HR=0.97 (0.7–1.36)
p=0.006
Raskob GE et al, N Engl J Med 2018;378:615–624
Time to Recurrent VTE, Major Bleeding and Survival
Recurrent VTE Major Bleeding Event-free Survival
HR=0.71 (0.48–1.06) HR=1.77 (1.03–3.04) HR=0.93 (0.77–1.11)
p=0.09 p=0.04 p=NS
E 7.9% vs D 11.3%
E 6.9% vs D 4.0%
E 55.0% vs D 56.5%
Raskob GE et al, N Engl J Med 2018;378:615–624
11
446
0
5
10
15
20
25
Recurrent VTE Major bleeding
Cum
ulat
ive
rate
at
6 m
onth
s (%
)
Dalteparin (n=203) Rivaroxaban (n=203)
11.3
4.0
7.9 6.9
0
5
10
15
20
25
Recurrent VTE Major bleeding
Inci
denc
e at
12
mon
ths
(%)
Dalteparin (n=522) Edoxaban (n=524)
NOACs for the Treatment of CAT
select-d1*
No cross-comparison intended
*select-d: multicentre (UK), prospective, randomized, open-label, pilot trial (N=406). Cumulative rate of CRNM bleeding at 6 months: 4% (dalteparin) versus 13% (rivaroxaban; HR=3.76; 95% CI 1.63–8.69); #Hokusai-VTE-Cancer: multinational, prospective, randomized, open-label, blinded endpoint, non-inferiority trial (N=1050).2,3 Primary outcome (mITT): composite of recurrent VTE or major bleeding during the 12 month study period (HR=0.97; 95% CI 0.70–1.36). Incidence of CRNM bleeding at 12 months: 11.1% (dalteparin) versus 14.6% (edoxaban; HR=1.38; 95% CI 0.98–1.94)2
1. Young A et al, J Clin Oncol 2018;36:2017–2023; 2. Raskob GE et al, N Engl J Med 2018;378:615–624; 3. Van Es N et al, Thromb Haemost 2015;114:1268–1276
Hokusai-VTE-Cancer2,#
HR=0.43 (95% CI 0.19–0.99)
HR=1.83 (95% CI 0.68–4.96)
HR=0.71(95% CI 0.48–1.06);
p=0.09 HR=1.77(95% CI 1.03–3.04);
p=0.04
CAT, cancer-associated thrombosis; GI, gastrointestinalKraaijpoel N et al, Thromb Haemost 2018;118:1439–1449
Hokusai-VTE: Bleeding GI Versus Non-GI Cancers
10
15
20
Maj
or b
leed
ing
even
t (%
)
Number of on-treatment days0 30 60 90 120 150 180 210 240 270 300 330 360
EdoxabanDalteparin
5
0
Patients with GI cancer Patients with non-GI cancer
Number at risk
Edoxaban 357 315 284 271 255 234 220 190 179 171 144 123 88Dalteparin 384 347 305 278 254 236 216 151 138 131 108 95 63
150120
10
15
20
Maj
or b
leed
ing
even
t (%
)
Number of on-treatment days0 30 60 90 180 210 240 270 300 330 360
EdoxabanDalteparin
5
0
Number at risk
Edoxaban 165 134 121 108 97 89 79 70 64 59 48 38 28Dalteparin 140 123 116 108 94 89 79 67 60 54 48 40 25
High risk
Active GI or urothelial tumours
Canadian Expert Consensus GuidelineCAT without contraindication to anticoagulation
(both incidental and symptomatic; lower-limb DVT and PE)
Risk of bleeding?(Consider well-documented risk factors for bleeding including GI toxicity
[i.e. GI co-morbidity, previous GI bleed, treatment-associated with GI toxicity], thrombocytopenia [<50,000 platelets/ml/min], renal impairment [GFR per the
Cockcroft–Gault formula of 30–50 ml/min], recent and/or life-threatening bleeding, intracranial lesion and use of antiplatelet agents)
Type of cancer?
DDIs with NOACs based on pharmacist-led PK review?
LMWH NOAC*
Other factors to consider:– Patient preference, after informing patient of
risks and benefits– Drug coverage– Body weight (consider LWMH in patients with
BMI >40 kg/m2 or weight >120 kg)– Burden of cancer (e.g. recurrence or
progression) and burden of VTE (consider LMWH for patients with severe symptoms, e.g. iliofemoral DVT, extensive PE, submassive PE, any thrombolysed patient)
– Renal impairment (consider LMWH for patients with GFR per the Cockcroft–Gault formula of 30–50 ml/min)
– Significant GI surgery or absorption disorders (consider LMWH for patients with impaired GI absorption)
– Pre-existing conditions and co-medication (e.g., ASA, other antiplatelet medications)
Non-high risk
Other types, non-active GI/urothelial tumours
No
Reassess on a regular basis (at least every 3 months if there are changes in management or patient condition)
Cancer status: still active? Consider stopping
Yes
Yes No
*Currently, edoxaban and rivaroxaban are the only NOACs with RCT evidence in CAT, with the evidence base stronger for edoxabanBMI, body mass index; CAT, cancer-associated thrombosis; DDI, drug-drug interaction; DVT, deep veinthrombosis; GFR, glomerular filtration Rate; GI, gastrointestinal, LMWH, low molecular weight heparin; PE, pulmonary embolism; UFH, unfractionated heparin
Adapted from Carrier M et al, Curr Oncol 2018;25:329–337
2019 ASCO Guidelines for the Treatment of CAT
Initial anticoagulation (5–10 days)
Long-term anticoagulation (<6 months)
Extended anticoagulation (≥6 months)
LMWH, edoxaban or rivaroxaban for at least 6 months is preferred because of their improved efficacy over VKAs
VKAs are an acceptable alternative for long-term therapy if LMWH or DOACs are not available
LMWH, DOACs or VKAs for extended anticoagulation beyond 6 months may be considered for selected patients* with active cancer
Initial anticoagulation may involve LMWH, UFH, fondaparinux or rivaroxaban
LMWH is preferred over UFH for the initial 5–10 days of anticoagulation for the patient with cancer with newly diagnosed VTE who does not have severe renal impairment (defined as creatinine clearance <30 ml/min)
*Such as those with metastatic disease or receiving chemotherapy
Key NS et al, J Clin Oncol 2019; doi: 10.1200/JCO.19.01461
Summary of Recent Guidelines/Guidance for the Treatment of CAT
ISTH SSC 20181 NCCN 20192 ASCO 20193
Anticoagulant choice NOACs (edoxaban and rivaroxaban) and LMWH are the preferred agents
Choice dependent on the risk of bleeding (LMWH preferred in patients with a high risk of bleeding) and potential for DDIs
Lists appropriate monotherapy/combined therapy options, including edoxaban, rivaroxaban and apixaban
Initial anticoagulation (first 5–10 days): LMWH or rivaroxaban preferred
Long-term (<6 months): LMWH, edoxaban or rivaroxaban (VKAs are acceptable alternatives for long-term therapy if LMWH/DOACs aren’t available)
Extended therapy (≥6 months): LMWH, edoxaban or rivaroxaban or VKAs
Duration of therapy No recommendations provided
No recommendations provided
Extended therapy beyond 6 months can be considered for select patients with active cancer
1. Khorana AA et al, J Thromb Haemost 2018;16:1891–1894; 2. NCCN guidelines v. 1.2019 (accessed 18 Apr 2019); 3. Key NS et al, J Clin Oncol 2019; doi: 10.1200/JCO.19.01461
What Are the Implications of These New Guidelines?
NOACs are now clearly an option for the treatment of cancer-associated VTE ‘One size fits all’ approach (e.g., LMWH for everyone) is no longer appropriate Patient selection is key, incorporating bleeding risk/renal function/
drug–drug interactions CAT treatment is not any more a ‘baseline assessment’ exercise Patient preferences should be considered
Thank You