1. Clinical Professor in Palliative Medicine
Patient-centered treatment of cancer associated VTE. Does one size fit all?
Simon Noble
Clinical Professor in Palliative Medicine
Cardiff University

5. Management of CAT Should be guided by best available evidence
Where evidence lacking management should be guided by an appreciation of
Pathophysiology of CAT
Thrombogenicity of respective cancer
Thrombogenicity of respective chemotherapy
Bleeding risks
Patient views

6. Schön’s swamp

7. Factors in decision making
Heuristics
Patient preference
Evidence

8. Heuristics
Simple, efficient rules which people often use to form judgments and make decisions
“rule of thumb”
Mental shortcuts

9. Heuristics
Simple, efficient rules which people often use to form judgments and make decisions
“rule of thumb”
Mental shortcuts
May be prone to bias
Availability
Representativeness
Anchoring and adjustment

10. Availability
The ease with which a particular idea can be brought to mind.
When considering likelihood of something happening we are often using availability heuristic
When considering infrequent events we may overestimate outcome likelihoods

11. The heterogeneity of Elvis Presley

12. Areas of uncertainty
Anticoagulation beyond 6 months in patients with active cancer
Within populations omitted from clinical trials
Extremes of weight
Brain metastases
Bleeding
Poor prognosis
Poor performance status
Choice of anticoagulant: LMWH vs coumarin vs DOAC

13. Clinical decision making in the swamp
Appreciation of the data in the less representative population
Appreciation of the heterogeneity of cancer
Discussion with patients regarding their wishes

14. The CLOT Trial Primary outcome: VTE recurrence
Risk reduction = 52%
HR 0.48 (95% CI 0.30, 0.77)
log-rank p = 0.002
NNT = 13
HR = hazard ratio; NNT = number needed to treat; VKA = vitamin K antagonist; VTE = venous thromboembolism
Lee AY et al. N Engl J Med 2003;349(2):146‒153.

15. LMWH vs warfarin meta analysis

16. What about DOACs?

17. DOACs in the treatment of CAT
NOAK: 32
VKA: 51
RR: 0,63
Recurrent VTE
Recurrent VTE
Lee A et al 2015: 12.7%
Recurrent VTE warfarin
Lee A et al. 2003: 16%
Meyer G et al %
Pooled incidence rates: 4.1% (2.6–6.0) for DOACs
6.1% (4.1–8.5) for VKAs [RR 0.66 (0.38–1.2)]
Major bleeding or CR-NMB
Reference:
van der Hulle T, den Exter PL, et al. Meta-analysis of the efficacy and safety of new oral anticoagulants in patients with cancer-associated acute venous thromboembolism. J Thromb Haemost 2014;12(7):1116–1120.
van der Hulle T et al. J Thromb Haemost CRNMB = clinically-relevant non-major bleeding

18. Proportion of metastatic patients
STUDY
LMWH
WARFARIN
RIVAROXABAN
CLOT
66%
69%
LITE
47%
36%
CATCH
55%
54%
ONCENOX
52%
EINSTEIN DVT/PE
26%
19%

19. Initial treatment of CAT
Heuristics
Patient preference
Evidence

20. Initial treatment of CAT
Heuristics
Patient preference
Evidence
LMWH

21. Treatment beyond six months
Heuristics
Patient preference
Evidence

22. Factors influencing decision whether to extend anticoagulation in CAT
Favors continuing anticoagulation
Favors stopping anticoagulation
Patient preference
10 concern recurrence
10 concern hemorrhage
Malignancy specific
Active malignancy
High risk cancer e.g., lung
Ongoing chemo or ESA
No evidence of disease
Low risk cancer e.g., breast
Previous history of VTE
Yes No
Nature of initial VTE
Life-threatening PE
DVT with severe postphlebitic syndrome
Non life-threatening PE
No residual symptoms
Risk of hemorrhage
Additional risk factors
Obesity
Sex
Poor performance status
Central venous catheter
Risk factors other than malignancy when diagnosed e.g., surgery
Reference:
Zwicker JI, Bauer KA. How long is long enough? Extended anticoagulation for the treatment of cancer-associated deep vein thrombosis. J Clin Oncol 2014;32(32):3596–3599.
10 = primary; CAT = cancer-associated thrombosis; DVT = deep vein thrombosis; ESA = erythropoiesis stimulating agent; PE = pulmonary embolism
Zwicker JI, Bauer KA. J Clin Oncol (32):3596–3600.

23. Treatment beyond six months
Heuristics
Patient preference
Evidence
LMWH
VKA
DOAC

24. Recurrent VTE management
Heuristics
Patient preference
Evidence

25. Treatment beyond six months
Heuristics
Patient preference
Evidence

26. Treatment beyond six months
Heuristics
Patient preference
Evidence
EMPIRICAL INCREASE LMWH
BD DOSING
Anti-Xa monitoring

27. End of life
Heuristics
Patient preference
Evidence

28. PPT Template Notes
Interference with cancer treatment is the most important attribute to patients, followed by efficacy of VTE therapy
* Impact / weight of each attribute on the overall preference / choice behavior
n = 100

29. To conclude Strong evidence for LMWH in first 3-6 months
Data limited beyond that
Several options available
Our decisions need to be carefully considered and made in partnership with the patient

30. Thank You
THANK YOU