Presentation is loading. Please wait.

Presentation is loading. Please wait.

Soirée AERIO 23 novembre 2011 Joseph GLIGOROV APHP Tenon.

Similar presentations


Presentation on theme: "Soirée AERIO 23 novembre 2011 Joseph GLIGOROV APHP Tenon."— Presentation transcript:

1 Soirée AERIO 23 novembre 2011 Joseph GLIGOROV APHP Tenon

2 Conflict of interest Involved in past 2 years in clinical trials financially supported & medical advisory boards Astra-Zeneca Bristol Myers Squib Eisai Glaxo Smith Kline Pfizer Roche Sanofi-Aventis

3 ADJUVANT TREATMENT pT1cpN0M0 luminal B TAM vs AI vs NAT
Joseph GLIGOROV APHP Tenon

4 LEVEL OF EVIDENCE: ?

5 DDFS by histological grade, ER content, erbB2 protein expression, and erbB2 amplification status.
DDFS by histological grade, ER content, erbB2 protein expression, and erbB2 amplification status. Left panels, tumor diameter 1–10 mm; right panels, 11–20 mm. Joensuu H et al. Clin Cancer Res 2003;9: ©2003 by American Association for Cancer Research

6 Tumor Size for NN T1 and T2 Cases in SEER database
2 4 6 8 10 12 20 30 40 50 % of cases There is more arbitrariness and inaccuracy in the measurement of a number of “Classical” parameters than is generally appreciated. Here we see in data from SEER how tumor size is generally reported in 5 mm increments with evidence of rounding up and down measured values. Tumor Size (mm)

7 Influence des traitements systémiques…
Données de registre

8 Survie globale et survie sans récidive durant les deux périodes

9 Survie sans récidive à distance
durant les deux périodes en fonction du pT1

10

11 Survie sans récidive à distance durant les deux périodes
en fonction du statut RH et de la prolifération

12 AIs Are Now the Adjuvant Endocrine Therapy of Choice for Postmenopausal Women With Breast Cancer
ASCO (2010)1 and NCCN (2011)2 5 years of endocrine therapy: Upfront AI or sequential TAM  AI St. Gallen Consensus Panel (2009)3 In view of BIG 1-98 sequencing results,4 the majority of the panel preferred upfront AI, particularly for patients at higher risk of early relapse St. Gallen Consensus Panel (2011)5-6 Panel was evenly divided regarding whether all patients should receive AI vs TAM therapy and if the AI should be upfront Regional guidelines in France and Germany support AI therapy7 ESMO (2010)8 Upfront AI for 5 years For patients receiving TAM, switch to AI after 2 to 3 years Total duration of therapy: 5 to 10 years 1. Burstein HJ, et al. JCO. 2010;28(23): ; 2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. v ; 3. Goldhirsch A, et al. Ann Oncol. 2009;20(8): ; 4. Mouridsen H, et al. NEJM. 2009;361(8): ; 5. Goldhirsch A, et al. Ann Oncol. 2011; 22(8): ; 6. Gnant M, et al. Breast Care. 2011; 6: ; 7. Wolters R, et al. Eur J Cancer July 7 Epub; 8. Aebi S, et al. Ann Oncol. 2010;21(suppl 5):v9-v14. 12

13 Adjuvant Therapy Trial Designs: Are Upfront AIs Superior to TAM?
Upfront (early adjuvant at start) Supporting Trials ATAC (ANA vs TAM) BIG 1-98 monotherapy arms (LET vs TAM) TEAM (2.75-year follow-up; EXE vs TAM) Randomization Supporting Trials ABCSG-8 alone (arms A & C) BIG 1-98 sequencing arms (arms C & D) TEAM (5-year follow-up) Sequencing Randomization A B C D Supporting Trials IES ITA ARNO/ABCSG-8 combined analysis Switching a Randomization All support switch to AI vs continued TAM1 Extended Adjuvant Supporting Trials MA-17 ABCSG-6 Randomization All support extended AI vs no further therapy2,3 a a Note that some patients from the original newly diagnosed population are lost because of recurrence or adverse events before randomization. Abbreviations: AI, aromatase inhibitor; ANA, anastrozole; EXE, exemestane; LET, letrozole; TAM, tamoxifen. 1. Dowsett M, et al. JCO. 2010;28(3): ; 2. Ingle JN, et al. Ann Oncol. 2008;19(5): ; 3. Jakesz R, et al. JNCI. 2007;99(24): 13

14 Patient Characteristics: BIG 1-98, ATAC, and TEAM
LET TAM ANA EXE n 4,003 4,007 3,125 3,116 4,898 4,868 Mean age, years 61 64.1 65 64 Tumor > 2 cm, % 36.5 37.7 35.3 36.4 40 Node+, % 41.5 41.2 34.9 33.5 47 ER+ and/or PgR+, % 99.8 99.7 83.7 83.4 100 Previous/adjuvant CT, % 25.3 22.3 20.8 36 Patient populations typical of PMW with early breast cancer in both trials AI arms are well matched to TAM control arms in both trials Patients with receptor-positive tumors BIG 1-98: 99.8% (study requirement) TEAM: 100% (study requirement) ATAC: 83.7% Abbreviations: AI, aromatase inhibitor; ANA, anastrozole; CT, chemotherapy; ER, estrogen receptor; EXE, exemestane; LET, letrozole; PgR, progesterone receptor; PMW, postmenopausal women; TAM, tamoxifen. 1. Thürlimann B, et al. NEJM. 2005;353(26): ; 2. Baum M, et al. Lancet. 2002;359(9324): ; 3. van de Velde CJH, et al. Lancet. 2011;377(9762): 14

15 Primary Efficacy Analyses: BIG 1-98, ATAC, and TEAM
Follow-up, months 26 100 60 HR P value DFS 0.81 .003 0.85 0.97 .604 Time to recurrence 0.72 <.001 0.76 0.94 .293 Time to distant recurrence 0.73 .001 0.84 .022 0.93 .30 BIG 1-98: LET significantly  DFS and time to distant recurrence at 26 months ATAC: No significant difference in distant metastasis until 100 months TEAM: No difference in DFS or time to recurrence between treatment arms at 60 months Abbreviations: DFS, disease-free survival; HR, hazard ratio; LET, letrozole. 1. Thürlimann B, et al. NEJM. 2005;353(26): ; 2. Forbes JF, et al. Lancet Oncol. 2008;9(1):45-53; 3. van de Velde CJH, et al. Lancet. 2011;377(9762): 15

16

17

18

19

20

21

22 DDFS by histological grade, ER content, erbB2 protein expression, and erbB2 amplification status.
DDFS by histological grade, ER content, erbB2 protein expression, and erbB2 amplification status. Left panels, tumor diameter 1–10 mm; right panels, 11–20 mm. Joensuu H et al. Clin Cancer Res 2003;9: ©2003 by American Association for Cancer Research

23 Is no adjuvant treatment a reasonable option ?

24 METASTATIC TREATMENT Triple negative disease
Joseph GLIGOROV APHP Tenon

25 LEVEL OF EVIDENCE: ?

26

27 Natural Histoty & Prognosis
Prat A, Perou CM. Molecular Oncology 2011

28

29 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

30 Overall Survival, Pooled Population
Non-BV (n=1008) BV (n=1439) Median, mo 26.4 26.7 HR (95% CI) 0.97 (0.86–1.08) 1-yr survival rate (%) 77 82 Bv=bevacizumab, CI=confidence interval. BV administered at 10 mg/kg/2wk in E2100 and bevacizumab 15 mg/kg/3wk in AVADO and RIBBON-1. Non-Bv=chemotherapy alone in E2100 and chemotherapy+placebo in AVADO and RIBBON-1. Data cutoff date was April 30, 2009 for AVADO and February 23, 2009 for RIBBON-1. 30 30

31 Analysis of OS by Subgroups
BV=bevacizumab, CI=confidence interval, ER=estrogen receptor, PR=progesterone receptor. Updated overall survival data with cutoff date of April 30, 2009 for AVADO and February 23, 2009 for RIBBON-1 was used for this analysis. 31 31 31

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

33 Progression-Free Survival, Pooled Population
Non-BV (n=1008) BV (n=1439) Median, mo 6.7 9.2 HR (95% CI) 0.64 (0.57–0.71) The docetaxel+BV7.5 arm in AVADO was excluded from the pooled analysis. PFS data for patients who received non-protocol anti- cancer therapies prior to disease progression were censored. The primary analysis of PFS was based on IRF assessment for E2100 and on investigator assessment for AVADO and RIBBON-1. 33

34 Analysis of PFS by Subgroups
BV=bevacizumab, CI=confidence interval, ER=estrogen receptor, PR=progesterone receptor. Updated overall survival data with cutoff date of April 30, 2009 for AVADO and February 23, 2009 for RIBBON-1 was used for this analysis. 34 34 34

35 Méta analyse bévacizumab 1ère ligne:
Amélioration de la PFS dans la population Triple négative (mais aussi RH+) Ayant reçu au préalable une chimiothérapie par taxanes en situation non métastatique Indépendament du type de chimiothérapie associée Paclitaxel capécitabine

36 Comparison of Subgroup Analyses of PFS from Three Phase III Studies of Bevacizumab in Combination with Chemotherapy in Patients with HER2-Negative Metastatic Breast Cancer Joyce O’Shaughnessy,1 Véronique Diéras,2 John Glaspy,3 Adam Brufsky,4 Kathy D. Miller,5 David W. Miles,6 Piotr Koralewski,7 See-Ch un Phan,8 Suman Bhattacharya8 1Baylor-Sammons Cancer Center, Texas Oncology, U.S. Oncology, Dallas, TX; 2Institut Curie, Paris, France; 3UCLA TORI, Los Angeles, CA; 4University of Pittsburgh, Pittsburgh, PA; 5Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; 6Mount Vernon Cancer Centre, London, England; 7Rydygiera Hospital, Krakow, Poland; 8BioOncology, Genentech, South San Francisco, CA

37 Overall PFS Results

38 Neoadjuvant or Adjuvant Taxane Treatment

39 Triple Negative

40

41

42

43 Y a t’il d’autres arguments cliniques ?
Cancers du sein dit « Triple négatif » Y a t’il d’autres arguments cliniques ?

44

45

46

47

48

49

50

51 Et en dehors des essais… dans la vrai vie…
Cancers du sein dit « Triple négatif » Et en dehors des essais… dans la vrai vie…

52 ATHENA Efficacité d’Avastin / sous groupe TNBC
Thomssen et al. SABCS 2009

53 Miles D et al. ESMO 2010

54 Conclusion En attendant les résultats d’autres études comportant des thérapies ciblées: l’association bévacizumab et chimiothérapie est la seul ayant démontré un bénéfice en PFS sans majoration considérable de la toxicité dans la population dite « triple négative » Et plus particulièrement chez des patientes pré-exposées aux taxanes en situation (néo)adjuvante ce qui correspond aujourd’hui à nos pratiques les plus courantes

55 Personalizing Cancer Care

56 I Bergman The 7th Seal

57 The complexity of TNBC treatment strategies
Thanks


Download ppt "Soirée AERIO 23 novembre 2011 Joseph GLIGOROV APHP Tenon."

Similar presentations


Ads by Google