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Other endpoints in screening studies for Soft Tissue Sarcomas

Other endpoints in screening studies for Soft Tissue Sarcomas. Jaap Verweij MD.PhD Dept of Medical Oncology Erasmus University Medical Center Rotterdam The Netherlands. Time. Surrogate Endpoint. Time. Disease. True Clinical Outcome. Intervention. Surrogate Endpoint. True Clinical

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Other endpoints in screening studies for Soft Tissue Sarcomas

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  1. Other endpoints in screening studies for Soft Tissue Sarcomas Jaap Verweij MD.PhD Dept of Medical Oncology Erasmus University Medical Center Rotterdam The Netherlands

  2. Time Surrogate Endpoint Time Disease True Clinical Outcome

  3. Intervention Surrogate Endpoint True Clinical Outcome Disease

  4. Question: If you know of all these ……… (Your Markers!) Would you be able to cure metastatic soft tissue sarcoma (your ultimate aim)? This is just a random selection of photographs. I apologize to anyone who is not listed

  5. Intervention Surrogate Endpoint True Clinical Outcome Disease

  6. p = 0.02 We Should Desist Using RECIST at Least in GIST Robert S. Benjamin, M.D. Department of Sarcoma Medical Oncology The SARCOMA Center

  7. It is easier to splice an atom than a prejudiceA.Einstein

  8. ? • How can we find the proof of concept: • early • when tumors do not shrink with treatment

  9. Screening for new drugs in STS • Are we looking at the right spot?

  10. Which endpoint to use in screening for new agents? • Response rate • Progression Free Rate • Progression Arrest Rate • TTP ratio

  11. Response Rate • Advantage: • Response relatively easily measurable • Disadvantage: • Does not take duration into account (DTIC 17%, duration 10 weeks) • Several cytotoxics discarded for response rate, but high SD rate • May not be appropriate for new cytostatic agents

  12. Hypothetical tumor evolution during treatment

  13. Is stable disease a relevant achievement? i.e: CR+PR+SD vs PD

  14. Progression free rate(2nd line treatment) 100 90 80 70 60 50 40 30 20 10 0 (months) 0 3 6 9 12 15 O N Number of patients at risk : 221 234 47 16 5 1 Inactive agents 136 146 55 18 14 11 Active agents Van Glabbeke et al, EJC 38:543-549,2002

  15. Type of drug N 3 months 6 months Estim. SE Estim. SE Inactive 234 21 % 3 % 8 % 2 % Active 146 39% 4 % 14% 3% All patients 380 28 % 3 % 10 % 2 % Progression free rates (2nd line) Van Glabbeke et al, EJC 38:543-549,2002

  16. Hypothetical tumor evolution during treatment TTP1 TTP2 If TTP2/TTP1 > 1.33: potentially active agent* * Mick et al, Contr.Clin.Trials 21:343-359. 2000

  17. ET-743 as 3rd line treatment inj soft tissue sarcoma Total population Patients without tumor regression but long lasting stable disease ASCO 2003, # 3293

  18. The problem of duration • It could take long to assess • And in screening studies we would like to know early

  19. Using progression rate Set maximum PD rate above which agent will be rejected PD rate of interest will depend on tumor type Tumor RR PD rate breast >30% <20% NSCLC >20% <30% Glioma >10% <40% STS >10% <50% (??)

  20. Progression Arrest* Rates % * Van Oosterom, In: Clinical Management of soft tissue sarcomas. Martinus Nijhoff Publishers, 131-138, 1986

  21. Progression Arrest Rates %

  22. Response versus Symptom benefit rate* Gefitinib in NSCLC Imatinib in GIST

  23. Conclusions Aim of screening studies • To estimate a.s.a.p.if a drug may be useful for patients Endpoint for screening studies • Progression free rates • Progression arrest rates • TTP ratio • Symptom improvement? All of these require proper validation

  24. Thank you for your attention

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