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Azienda ULSS 13 – Mirano VE

MULTIPLE TREATMENT CHOICES: ARE THEY EQUALLY ( cost ) EFFECTIVE?. Giovanni L. Pappagallo (giovanni.pappagallo@tin.it). Azienda ULSS 13 – Mirano VE. Dipartimento di Scienze Mediche U.O.C. di Oncologia & Ematologia Oncologica. Ufficio di Epidemiologia & Sperimentazioni Cliniche.

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Azienda ULSS 13 – Mirano VE

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  1. MULTIPLE TREATMENT CHOICES: ARE THEY EQUALLY (cost) EFFECTIVE? Giovanni L. Pappagallo (giovanni.pappagallo@tin.it) Azienda ULSS 13 – Mirano VE Dipartimento di Scienze Mediche U.O.C. di Oncologia & Ematologia Oncologica Ufficio di Epidemiologia & Sperimentazioni Cliniche

  2. YOUR TREATMENT CHOICE… Statistical Significance vs Clinical Significance Registrative Studies vs Therapeutic Strategies Controlling the Cost of Innovative Cancer Therapeutics

  3. YOUR TREATMENT CHOICE… Statistical Significance vs Clinical Significance RegistrativeStudies vs TherapeuticStrategies Controlling the Costof Innovative CancerTherapeutics

  4. A. Stone & K. Carroll, ASCO 2008

  5. A. Stone & K. Carroll, ASCO 2008

  6. PoorClinicalSignificancewhen PossibleClinicalSignificancealsowhen P<0.05 • Earlytermination • Overpowering • Inadequatecontrolgroup • Inadequate (?) primaryendpoint • Subgroupanalysis • P≥0.05 • Underpowering • Inadequate(?) patientselection

  7. RL Schilsky, ASCO 2005

  8. RL Schilsky, ASCO 2005

  9. J Slutsman, ASCO 2005

  10. J Slutsman, ASCO 2005

  11. target Δ of HERA trial: RRR 23% HR 0.54 (95%CL 0.43-0.67) Trastuzumab better Control better J Slutsman, ASCO 2005

  12. HR 0.62 (95%CL 0.41-0.95) target Δ of CALGB 9633: RRR 33% CarboTaxol better Control better J Slutsman, ASCO 2005

  13. PoorClinicalSignificancewhen PossibleClinicalSignificancealsowhen P<0.05 • Earlytermination • Overpowering • Inadequatecontrolgroup • Inadequate (?) primaryendpoint • Subgroupanalysis • P≥0.05 • Underpowering • Inadequate(?) patientselection

  14. Target Δ: HR erlotinib:placebo = 0.75 (2 months OS improvement) Analysis after 381 events (450 patients; α 5%, power 80%) Analysis after 486 events (569 patients) Actual difference: 0.33 months (10 days)

  15. Target Δ: HR cetuximab:placebo = 0.80 (2.5 months OS improvement) Analysis after 845 events (1100 patients; α 5%, power 90%) Analysis after ??? events (1125 patients) Actual difference: 1.2 months

  16. PoorClinicalSignificancewhen PossibleClinicalSignificancealsowhen P<0.05 • Earlytermination • Overpowering • Inadequatecontrolgroup • Inadequate (?) primaryendpoint • Subgroupanalysis • P≥0.05 • Underpowering • Inadequate(?) patientselection

  17. “Standard” therapy? Equipoise?

  18. Equipoise? “Standard” therapy?

  19. Equipoise? New “standard”? “Standard” therapy?

  20. S.D. Averbuch, ASCO 2008

  21. PoorClinicalSignificancewhen PossibleClinicalSignificancealsowhen P<0.05 • Earlytermination • Overpowering • Inadequatecontrolgroup • Inadequate (?) primaryendpoint • Subgroupanalysis • P≥0.05 • Underpowering • Inadequate(?) patientselection

  22. F. Pignatti, ESMO 2008

  23. VALIDATION OF SURROGATE ENDPOINTS:“FULL CAPTURE OF EFFECT” Effect of treatment on surrogate Effect of surrogate on true endpoint S T Trt Effect of treatment on trueendpoint must befullycaptured by surrogate Prentice, Statist Med 1989;8:431.

  24. VALIDATION OF SURROGATE ENDPOINTS:“FULL CAPTURE OF EFFECT” Effect of treatment on surrogate Effect of surrogate on true endpoint S T Trt Effect of treatment on trueendpoint must befullycaptured by surrogate Prentice, Statist Med 1989;8:431.

  25. PoorClinicalSignificancewhen PossibleClinicalSignificancealsowhen • P≥0.05 • Underpowering • Inadequate(?) patientselection P<0.05 • Earlytermination • Overpowering • Inadequatecontrolgroup • Inadequate (?) primaryendpoint • Subgroupanalysis

  26. AO Sartor

  27. A. Gennari, 2008

  28. S.L. George

  29. F. Cappuzzo, WCLC 2009

  30. PoorClinicalSignificancewhen PossibleClinicalSignificancealsowhen P<0.05 • Earlytermination • Overpowering • Inadequatecontrolgroup • Inadequate (?) primaryendpoint • Subgroupanalysis • P≥0.05 • Underpowering • Inadequate(?) patientselection

  31. PoorClinicalSignificancewhen PossibleClinicalSignificancealsowhen P<0.05 • Earlytermination • Overpowering • Inadequatecontrolgroup • Inadequate (?) primaryendpoint • Subgroupanalysis • P≥0.05 • Underpowering • Inadequate(?) patientselection

  32. E. Winer, St. Gallen 2009

  33. Breast-cancer deaths Other deaths Competing causes of mortality Age ≥50 years and ER+ Probability 0.4 0.3 0.2 0.1 0.0 0 5 10 15 Time from diagnosis (years) ER+, oestrogen receptor-positive Hanrahan et al. J Clin Oncol 2007; 25: 4952-60

  34. E. Winer, St. Gallen 2009

  35. YOUR TREATMENT CHOICE… StatisticalSignificance vs ClinicalSignificance Registrative Studies vs Therapeutic Strategies Controlling the Cost of Innovative Cancer Therapeutics

  36. MAINTENANCE THERAPY IN ADVANCED NSCLC: PROOF OF PRINCIPLEOR READY-TO-USE STRATEGY? Only 19% of placebo ptsreceivedPemetrexed at anytime Only 16% of placebo ptsreceivedErlotinib at anytime C. Belani, ASCO 2009 F. Cappuzzo, WCLC 2009

  37. The Best 2ndLine (one of)The Best 1st Line

  38. YOUR TREATMENT CHOICE… StatisticalSignificance vs ClinicalSignificance RegistrativeStudies vs TherapeuticStrategies Controlling the Cost of Innovative Cancer Therapeutics

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