Patientcentered treatment of cancer associated VTE Does one

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 Evidence Patient preference

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) NNT = 13 log-rank p = 0. 002 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 Recurrent VTE 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)] Recurrent VTE warfarin Lee A et al. 2003: 16% Meyer G et al. 2002 17% Major bleeding or CR-NMB 17 van der Hulle T et al. J Thromb Haemost 2014. CRNMB = clinically-relevant non-major bleeding

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

Initial treatment of CAT Heuristics Evidence Patient preference

Initial treatment of CAT Heuristics H W M LEvidence Patient preference

Treatment beyond six months Heuristics Evidence Patient preference

Factors influencing decision whether to extend anticoagulation in CAT Favors continuing anticoagulation Factor 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 • No • Yes Additional risk factors • • Obesity Sex Poor performance status Central venous catheter • Risk factors other than malignancy when diagnosed e. g. , surgery 10 = primary; CAT = cancer-associated thrombosis; DVT = deep vein thrombosis; ESA = erythropoiesis stimulating agent; PE = pulmonary embolism 22 Zwicker JI, Bauer KA. J Clin Oncol 2014. 32(32): 3596– 3600.

Treatment beyond six months Heuristics H W LM A K V C Patient A Evidence O D preference

Recurrent VTE management Heuristics Evidence Patient preference

Treatment beyond six months Heuristics Evidence Patient preference

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

End of life Heuristics Evidence Patient preference

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

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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