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FRANCESCO BOCCARDO

FRANCESCO BOCCARDO. INIBITORI DELL’AROMATASI. (back from San Antonio). Professore Ordinario di Oncologia Medica, Università di Genova. Direttore Oncologia Medica B IST .Genova. Presidente Nazionale Associazione Italiana Oncologia Medica. Decision Points. Tamoxifen. Aromatase inhibitor.

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FRANCESCO BOCCARDO

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  1. FRANCESCO BOCCARDO INIBITORI DELL’AROMATASI (back from San Antonio) Professore Ordinario di Oncologia Medica, Università di Genova Direttore Oncologia Medica BIST .Genova Presidente Nazionale Associazione Italiana Oncologia Medica

  2. Decision Points Tamoxifen Aromatase inhibitor 5 years total 10 years total > 10 years 1 ? ? 4 3 ? 2 3 ? ? ? 4

  3. Decision Points:after 2-3 yrs of Tam IES ABCSG8/ARNO95 ITA ? 1 Tamoxifen ? Aromatase inhibitor 5 years total 10 years total > 10 years

  4. The Lancet 9561:533-5, 2007

  5. The Lancet 9561:533-5, 2007

  6. The Lancet 9561:533-5, 2007

  7. AIOG Metanalysis

  8. ……….back from San Antonio 2008: take home #1 “There is a clear benefit (including a S benefit) in switching women already on treatment with Tam to an AI (anastrozole,exemestane) unless AI therapy is contraindicated”

  9. Tamoxifen Aromatase inhibitor 5 years total 10 years total > 10 years Decision Points: Initial choice ? ? ATAC BIG 1-98 monotherapy TEAM 2.75 yr 2 ? ? ?

  10. ATAC:100 mos median follow-up , Lancet Oncology 2007

  11. AIOG Metanalysis

  12. : TEAM trial

  13. ……….back from San Antonio 2008: take home #2 “Three drugs now available as front line treatment: Which drug or which patients?”

  14. ATAC:100 mos median follow-up , Lancet Oncology 2007

  15. Predicting the benefit and the risks. Tamoxifen vs Ais: Tumor Profile ERPgR HER2 Recurrence Score Cyclin E uPA/uPAI-1 Bcl-2 ER-beta Patient Profile Osteoporosis Hypercholesterolemia CV risk factors Endometrial pathologies DVT & TE risk factors SSRI use CYP 19 Genotype CYP2D6 Genotype

  16. TRANSACT

  17. ABCSG 8

  18. ……….back from San Antonio 2008: take home #3 “Starting with an Ai is a reasonable choice especially in certain patient subsets (i.e. PgRneg,HER2 pos,HRScore Node neg,poor metabolizers of CYP2D6….!):however: 1) no major mortality advantge 2) No over rate in selecting patients “

  19. Decision Points:sequencing Tamoxifen Aromatase inhibitor 5 years total 10 years total > 10 years 1 ? ? 4 3 ABCSG8 TEAM 5-yr: n.a. yet ? 2 3 BIG-1-98 ? ? ? 4

  20. ABCSG Trial 8 Sequencing versus TAM Switch point Tamoxifen(3 years) Tamoxifen (2 years) Randomize Primarysurgery Tamoxifen (2 years) Anastrozole (3 years) Switching period Sequencing period Jakesz R, et al. Lancet. 2005;366:455-462.

  21. ABCSG 8 seq:Event-Free Survival following surgery (n = 2926) 100 94.4% 95 90 92.9% EFS (%) 85 Events T 101 T  A 79 HR 0.76 P Value .068 80 T T  A 75 0 0 12 24 36 48 60 72 Time Since Surgery (Months) Jakesz R, et al. 2005 SABCS. Abstract 13

  22. Sequencing versus LTZ

  23. Take home #3

  24. DOUBLE TRIAL Switch point Examestane(3 years) LTZ/ANA (2 years) Randomize Primarysurgery LTZ/ANA(2 years) LTZ/ANA(3 years) Switching period Sequencing period

  25. ……….back from S. Antonio 2008: Take home #4 “sequencing TAM with an Ai is probably better than TAM alone,but does not offer major advantages vs Ai alone; switching from an Ai to TAM is possible if required… “

  26. Decision Points:after 5 yrs of Tam NSABP B-14 ? MA.17 ABCSG6a Tamoxifen ? Aromatase inhibitor NSABP B-42 5 years total 10 years total > 10 years

  27. NSABP B-14: No Benefit of Extending Tamoxifen Beyond 5 Years DFS OS 100 100 94% 90 90 91% P = .07 82% P = .03 80 80 78% Percentage of Patients Percentage of Patients Placebo Tamoxifen Placebo Tamoxifen 70 70 60 60 50 50 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 Years Years • Tamoxifen demonstrated higher rates of endometrial cancer, and more deaths from ischemic heart disease and cerebrovascular disease Fisher B, et al. J Natl Cancer Inst. 2001;93:684-690.

  28. MA.17: Key Endpoints in Nodal Subgroups • Preplanned analysis (n = 5187) HR: 0.45 (0.27-0.75) HR: 0.63 (0.31-1.27) HR: 1.52 (0.76-3.06) Node* neg Node neg Node neg HR: 0.82 (0.57-1.19) Distant* DFS OS DFS* HR: 0.58 (0.45-0.76) HR: 0.61 Node* pos Node* pos Node*pos HR: 0.53 (0.36-0.78) HR: 0.61 (0.38-0.98) HR: 0.61 (0.45-0.84) *non statistically significant Goss PE, et al. J Natl Cancer Inst. 2005;97:1262-1271.

  29. Adjusted HR (PLAC-LET to PLAC) for Efficacy Outcomes :postumblinding Disease-free survival Distant disease-free survival Overall survival Contralateral breast cancer 0.6 0.53 0.5 p=0.05 P = .05 0.4 Hazard Ratio 0.31 0.28 0.3 0.23 p<0.0001 P < .0001 p=0.002 P = .002 0.2 p=0.012 P = .012 0.1 0 PLAC-LET to PLAC Goss PE, et al. SABCS 2005. Abstract 16.

  30. ………back from S.Antonio 2008: Take home #5 “ Late switching after 5 yrs of TAM: no news “

  31. Decision Points:after 5 yrs of AIs NSABP B-14 ? MA.17 Tamoxifen ? Aromatase inhibitor MA.17-R NSABP B-42 5 years total 10 years total > 10 years

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