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Post San Antonio & Post EBCC Chemotherapie Aafke H. Honkoop

Post San Antonio & Post EBCC Chemotherapie Aafke H. Honkoop. San Antonio BCS & EBCC. Presentaties Neoadjuvante chemotherapie (2) Adjuvante chemotherapie (4) Gemetastaseerde ziekte (2) Posters Neoadjuvante chemotherapie Adjuvante chemotherapie Nieuwe middelen

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Post San Antonio & Post EBCC Chemotherapie Aafke H. Honkoop

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  1. Post San Antonio &Post EBCCChemotherapie Aafke H. Honkoop

  2. San Antonio BCS & EBCC • Presentaties Neoadjuvante chemotherapie (2) Adjuvante chemotherapie (4) Gemetastaseerde ziekte (2) • Posters Neoadjuvante chemotherapie Adjuvante chemotherapie Nieuwe middelen Gemetastaseerde ziekte

  3. Neoadjuvante chemotherapie • Comparison of TAC versus NX in patients non-responding to 2 cycles of neoadjuvant TAC- first results of the phase III GEPARTRIO study by the German Breast Group • Primary endocrine therapy versus chemotherapy in postmenopausal ER-positive patients Semiglazov, et al

  4. Comparison of Dox/Doce/Cyclo (TAC) versus Vino/Cape ) (NX) in patients non-responding to 2 cycles of neoadjuvant TAC GEPARTRIO

  5. GEPARTRIO • Doseringen: TAC: 75/50/500 mg/m2 NX : 25 d1,8/2500 d1-14 • Eindpunten studie Echografische response Pathologische response

  6. GEPARTRIO

  7. GEPARTRIO, conclusies • 2/3 heeft uiteindelijk nog response op TAC • TAC meer toxiciteit (hematologisch als ook niet-hematologisch) • NX goed alternatief voor TAC

  8. Neoadjuvante endocriene therapie versus chemotherapie • T2N1, T3N1-0, T4NOMO (geen IBC) • ER+, postmenopausale patienten • AI versus Doxorubicine/Paclitaxel 60/200, q 3wkn • Eindpunten: Klinische response Echografische response Pathologische response mammasparende operatie Semiglazov, et al

  9. Neoadjuvante endocriene therapie versus chemotherapie

  10. Neoadjuvante endocriene therapie versus chemotherapie CONCLUSIES • Effectiviteit endocriene therapie gelijk aan chemotherapie • Endocriene therapie minder toxisch

  11. Adjuvante chemotherapie GEICAM 9906; 6xFEC versus 4xFEC -8xP q1wk 4xTC versus 4xAC , Jones et al. Houston INT C9741 Dose Dense INT E1199, 4xAC- P1, P3, D1 of D3

  12. Doce/Cyclo (TC) versus Dox/Cyclo (AC) in early breast cancer • N=1016, N0 en N+ • 4 x AC versus 4 x TC • Chemotherapie voor Radiotherapie • Tam na chemotherapie, indien ER+ • Eindpunten: DFS (primair) OS en Toxiciteit (secundair) Jones et al, Texas

  13. TC versus AC

  14. TC versus AC

  15. TC versus AC

  16. TC versus AC conclusies • TC betere DFS • TC minder toxiciteit • TC nieuwe standaard

  17. Five year follow-up of INT C9741: dose-dense is safe and effective

  18. INT C9741

  19. INT C9741

  20. INT C9741

  21. INT C9741

  22. INT C9741

  23. INT C9741

  24. INT C9741 conclusies • Dose Dense is superior • Geen verschil sequentieel versus gelijktijdig • Data stabiel t.o.v. 3 jaar geleden • Toxiciteit van DD acceptabel • Groter voordeel van DD bij ER-

  25. Phase III study of AC followed by P or D Q 1wk or Q 3wk in N+ and N0 high risk Patients: INT E1199

  26. INT E1199 • Eindpunten : DFS en OS • Vergelijking : P versus D Q1 versus Q3 P3 als standaard versus andere armen (subset ER- P3 versus andere armen) • Median follow-up: 46.5 mnd • N=4988

  27. INT E1199

  28. INT E1199

  29. INT E1199

  30. INT E1199

  31. INT E1199 conclusies • Docetaxel en Paclitaxel even effectief • Q1 wk gelijk aan Q3 wk • Trend voor een betere DFS P1 tov P3 (meer uitgesproken bij ER-) • D1 meer gr3/4 tox; 39% versus 24%

  32. GEICAM 99066xFEC versus 4xFEC- 8xP in N+ BC

  33. GEICAM 9906 • Eindpunten: DFS en OS • Vergelijking: 6xFEC90 4xFEC90 - 8xP 100 q1wk • Median follow-up: 47 mnd • N=1248

  34. GEICAM 9906

  35. GEICAM 9906

  36. Geicam 9906

  37. Geicam 9906 conclusies • Toxiciteit van beide schema’s acceptabel • FEC - P meer myalgie • FEC meer neutropenie • Adjuvant FEC - P effectiever in alle subgroepen tav DFS • Geen verschil in OS

  38. Gemetastaseerd mammacarcinoom • Meta-analyse eerste lijn Taxanen (Piccart) Hoge dosis chemotherapie (Rodenhuis)

  39. INCORPORATION OF TAXANES IN FIRST LINE CHEMOTHERAPY FOR ADVANCED BREAST CANCER : A META-ANALYSIS Presenter : Martine J. Piccart-Gebhart, MD, PhD Statisticians : Tomasz Burzykowski, PhD, Marc Buyse, ScD Clinical Fellows : Gul Atalay, Daniela Rosa Financial support : EORTC Breast Cancer Group

  40. In2002 • N = 12 trials with inconsistent results • Doxorubicin (8), Epirubicin (4) • Docetaxel (6), Paclitaxel (6) • Survival gain in only one trial (Jassem et al) • Greater toxicity and cost with the anthracycline + taxane regimens • Febrile neutropenia 8 – 21% (paclitaxel + A) 23 – 33% (docetaxel + A) • Cross-over rates 24 – 57%

  41. Individual patient data were collected (not merely summary statistics from the literature): • All relevant trials were included, whether published or not • Reporting biases were avoided • Data were extensively checked (and resulted in the exclusion of one trial) • The power of the analyses was maximized • Subgroup analyses (by visceral disease / ER status) could be performed

  42. Progression-free survival hazard ratios

  43. Overall survival hazard ratios

  44. Single agent doxorubicine (at 75 mg/m2) was better than single agent taxane in terms of response rate and PFS in one of 3 trials • Taxanes in combination with anthracyclines provide greater chances of "response" remain the treatment of choice when a "response" is desirable • The impact of taxanes on progression-free survival appears to be marginal and their impact on survival has not been shown by this meta-analysis of trials conducted in the "empirical" era of oncology • More attention needs to be paid to cross-over • Strong considerations should be given to trials run in better defined “molecular” sub-populations

  45. High-Dose Chemotherapyin Breast Cancer A ‘Critical Review’, or: Is it dead ? Rodenhuis

  46. High-dose Therapy in Breast Cancer: • in stage IV patients (phase II) Strong rationale derived from model systems • High objective response rates • Excellent DFS rate in high-risk primary breast cancer (phase II)

  47. 861 Stage IV Patients Randomized6 studies, 6 different HD regimens

  48. High-Dose Chemotherapy with PBPC-Tx in Advanced Breast Cancer • High-dose chemotherapy cannot eradicate macroscopic disease • It may (sometimes) eradicate micrometastases (when any macrometastatic disease is either resected or irradiated • ( ? but could this also be achieved by conventionally dosed chemotherapy ? )

  49. High-Dose Chemotherapy with PBPC-Tx in High-Risk Breast Cancer • Over5500 patients treated in 14 (reported) randomized studies • Many studies (allunderpowered, most too early for OS analysis) show trend for RFS benefit for dose-intensive arm

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