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

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

Schön’s swamp

Factors in decision making Heuristics Patient preference Evidence

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

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

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

The heterogeneity of Elvis Presley

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

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

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.

LMWH vs warfarin meta analysis

What about DOACs?

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. 2002 17% 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 2014. CRNMB = clinically-relevant non-major bleeding

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

Initial treatment of CAT Heuristics Patient preference Evidence

Initial treatment of CAT Heuristics Patient preference Evidence LMWH

Treatment beyond six months Heuristics Patient preference Evidence

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 2014.32(32):3596–3600.

Treatment beyond six months Heuristics Patient preference Evidence LMWH VKA DOAC

Recurrent VTE management Heuristics Patient preference Evidence

Treatment beyond six months Heuristics Patient preference Evidence

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

End of life Heuristics Patient preference Evidence

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

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

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