RUOLO DELLA TERAPIA ANTIANGIOGENICA NEL CARCINOMA MAMMARIO Rilevanza delle Evidenze Scientifiche - PowerPoint PPT Presentation

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RUOLO DELLA TERAPIA ANTIANGIOGENICA NEL CARCINOMA MAMMARIO Rilevanza delle Evidenze Scientifiche

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  1. RUOLO DELLA TERAPIA ANTIANGIOGENICA NEL CARCINOMA MAMMARIORilevanza delle Evidenze Scientifiche P Pronzato Modena, 18.11.2011

  2. (Anti-) Angiogenesis

  3. [TITLE]

  4. [TITLE]

  5. HER2- Metastatic Breast Cancer(CT Needed)Decision Making Problems

  6. F Cardoso & J Cortes

  7. F Cardoso & J Cortes

  8. F Cardoso & J Cortes

  9. F Cardoso & J Cortes

  10. MBC: main drivers in 2010s • Clinico Pathological Factors • HER2 /HR • Previous Treatment • Burden of Disease

  11. MBC: main drivers in 2010s • Goals • Prolongation of Survival • Quality of Life • Symptom Relief • Response • Delay of Progression • Clinico Pathological Factors • HER2 /HR • Previous Treatment • Burden of Disease

  12. Evidence Based Decision Making HER2- / MBC MBC Previous anthra-taxanes CT HER2 HER2- HER2+ HR+ HR- After HT CHEMOTHERAPY

  13. Evidence Based Decision Making HER2- / MBC MBC Previous anthra-taxanes CT HER2 HER2- HER2+ HR+ HR- After HT CHEMOTHERAPY

  14. [TITLE] MN Dickler, ASCO 2011

  15. RCTs and Meta-Analysis

  16. Survival Analyses Miller K et al. N Engl J Med 2007;357:2666-2676

  17. Hazard Ratios for Disease Progression Miller K et al. N Engl J Med 2007;357:2666-2676

  18. Hazard Ratios for Disease Progression Soon this regimen became widely adopted by clinicians who treated thousands of patients and felt confortable with using the drug AM Gonzalez-Angulo, Nat Rev Clin Oncol 2011 Miller K et al. N Engl J Med 2007;357:2666-2676

  19. Trial Design • Previously untreated MBC • (n=1237) • Stratification factors: • Disease-free interval • Previous adjuvantchemotherapy • No. of metastatic sites • Capecitabine, taxane or anthracycline Investigator’s choice of chemotherapy Chemotherapy +bevacizumabq3w Treat until PD Capecitabine or taxane/ anthracycline Optional2nd-line chemotherapy+ bevacizumab RANDOMIZE 2:1 Chemotherapy +placeboq3w • Capecitabine (1000 mg/m2 bid d1–14) • Taxane (docetaxel 75–100 mg/m2 or nab-paclitaxel 260 mg/m2) • Anthracycline-based chemotherapy • AC (doxorubicin 50–60 mg/m2, cyclophosphamide 500–600 mg/m2) • EC (epirubicin 90–100 mg/m2, cyclophosphamide 500–600 mg/m2) • FAC (5-FU 500 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2) • FEC (5-FU 500 mg/m2, epirubicin 90–100 mg/m2, cyclophosphamide 500 mg/m2) • Bevacizumab or placebo (15 mg/kg) NJ Robert, JCO 2011 Robert et al. ASCO 2009

  20. PFS: Capecitabine Cohort 1.0 0.8 0.6 0.4 0.2 0 PFS estimate 5.7 8.6 • 0 6 12 18 24 30 Months NJ Robert, JCO 2011 Robert et al. ASCO 2009 *Stratified analysis

  21. Objective Response Rate*: Capecitabine Cohort Patients, % Complete response Partial response p=0.0097 35.4 23.6 NJ Robert, JCO 2011 *Patients with measurable disease at baseline NJ Robert, JCO 2011 Robert et al. ASCO 2009

  22. A Meta-Analysis of Overall Survival Data from Three Trials of Bevacizumab and First-Line Chemotherapy as Treatment for Patients with Metastatic Breast Cancer Joyce O’Shaughnessy, David Miles, Robert Gray, Véronique Diéras, Edith A. Perez, Robin Zon, Javier Cortés, Xian Zhou, See-Chun Phan,Kathy Miller Baylor-Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, TX; Mount Vernon Cancer Centre, London, England; Dana-Farber Cancer Institute, Boston, MA; Institut Curie, Paris, France; Mayo Clinic, Jacksonville, Florida; Michiana Hematology Oncology, South Bend, IN; Vall d'Hebron University Hospital, Barcelona, Spain; BioOncology, Genentech, S San Francisco, CA; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN ASCO, 2010

  23. General Study Designs OptionalSecond-line Chemo + BV(AVADO and RIBBON-1 only) E2100Paclitaxel Chemo +No BV Treat until PD Previously Untreated MBC AVADO Docetaxel RANDOMIZE Chemo +BV RIBBON-1 Capecitabine, Taxane,orAnthracycline

  24. Comparison of the Studies BV=bevacizumab, PL=placebo, PFS=progression-free survival, ORR=objective response rate, OS=overall survival. * Permitted continuing on BV or crossing over to BV. †Analyses based on IRF assessments.

  25. Overview of Efficacy Results from the Individual Studies in the Pooled Analysis BV=bevacizumab, Cape=capecitabine, Tax/Anthra=taxane/anthracycline. * 15 mg/kg cohort.

  26. Patient Characteristics, Pooled Population

  27. Progression-Free Survival, Pooled Population

  28. Analysis of PFS by Subgroups

  29. Objective Response Rate* 50 Objective response rate (%) 45 49 40 35 30 32 25 20 15 10 5 0 Non-BV(n=788) BV (n=1105) *Includes only patients with measurable disease at baseline.

  30. Overall Survival, Pooled Population

  31. Use of Subsequent Systemic Therapies in AVADO and RIBBON-1 Studies* *Data not available from E2100.

  32. Conclusions Significant PFS advantage but no OS difference with BV across 3 first-line studies and in pooled analysis In MBC, the ability of Phase III trials to demonstrate treatment effect upon OS depends on the duration of survival post-progression (SPP) Higher chance of affecting OS in populations with short SPP (20 month PPS in these 3 first-line trials) Patients with adverse prognostic features benefit from BV as do patients with more indolent disease Low incidence of treatment-related deaths with BV Safety profile consistent with previous BV experience Broglio and Berry. 2009. J Natl Cancer Inst. 101:1642-49. Saad, Katz, and Buyse. 2010. J Clin Oncol. 28:1958-62. Burzykowski, et al.2008. J Clin Oncol. 26:1987-92.

  33. A look at TNBC

  34. [TITLE]

  35. [TITLE]

  36. [TITLE]

  37. Facts and Prejudices

  38. Regrowth • Toxicity • Age • Cost

  39. From discontinuation to death D Miles, JCO 2011

  40. Bevacizumab and FAEs V Ranpura, JAMA 2011

  41. Bevacizumab and FAEs V Ranpura, JAMA 2011

  42. Bevacizumab and CHF T Choueiri, JCO 2011

  43. Safety, Causes of Death* *Safety evaluable patient population.

  44. Grade ≥3 Selected Adverse Events (AEs), Pooled Population RPLS=Reversible posterior leukoencephalopathy syndrome.

  45. Grade ≥3 Selected Adverse Events (AEs), Pooled Population RPLS=Reversible posterior leukoencephalopathy syndrome.

  46. Elderly Patients X Pivot, EJC 2011

  47. TJ Smith, & BE Hillner, NEJM 2011

  48. Cost-Effectiveness

  49. Conclusions