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Soirée AERIO 23 novembre 2011 Joseph GLIGOROV APHP Tenon.

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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. Joensuu H et al. Clin Cancer Res 2003;9:923-930 ©2003 by American Association for Cancer Research

6 Tumor Size for NN T1 and T2 Cases in SEER database 0 2 4 6 8 10 12 01020304050 Tumor Size (mm) % of cases

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

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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 therapy 7 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):3784-3796; 2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. v.2.2011; 3. Goldhirsch A, et al. Ann Oncol. 2009;20(8):1319-1329; 4. Mouridsen H, et al. NEJM. 2009;361(8):766-776; 5. Goldhirsch A, et al. Ann Oncol. 2011; 22(8):1736-1747; 6. Gnant M, et al. Breast Care. 2011; 6:136-141; 7. Wolters R, et al. Eur J Cancer. 2011 July 7 Epub; 8. Aebi S, et al. Ann Oncol. 2010;21(suppl 5):v9-v14.

13 Adjuvant Therapy Trial Designs: Are Upfront AIs Superior to TAM? 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):509-518; 2. Ingle JN, et al. Ann Oncol. 2008;19(5):877-882; 3. Jakesz R, et al. JNCI. 2007;99(24):1845-1853. Supporting Trials ATAC (ANA vs TAM) BIG 1-98 monotherapy arms (LET vs TAM) TEAM (2.75-year follow-up; EXE vs TAM) Upfront (early adjuvant at start) 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 Extended Adjuvant Supporting Trials MA-17 ABCSG-6 a Randomization All support switch to AI vs continued TAM 1 All support extended AI vs no further therapy 2,3 13

14 Patient Characteristics: BIG 1-98, ATAC, and TEAM 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):2747-2757; 2. Baum M, et al. Lancet. 2002;359(9324):2131-2139; 3. van de Velde CJH, et al. Lancet. 2011;377(9762):321-331. BIG 1-98 1 ATAC 2 TEAM 3 CharacteristicsLETTAMANATAMEXETAM n4,0034,0073,1253,1164,8984,868 Mean age, years61 64.1 6564 Tumor > 2 cm, %36.537.735.336.440 Node +, %41.541.234.933.547 ER + and/or PgR +, %99.899.783.783.4100 Previous/adjuvant CT, %25.3 22.320.836 14

15 Primary Efficacy Analyses: BIG 1-98, ATAC, and TEAM 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):2747-2757; 2. Forbes JF, et al. Lancet Oncol. 2008;9(1):45-53; 3. van de Velde CJH, et al. Lancet. 2011;377(9762):321-331. BIG 1-98 1 ATAC 2 TEAM 3 Follow-up, months 2610060 HRP valueHRP valueHRP value DFS0.81.0030.85.0030.97.604 Time to recurrence0.72<.0010.76<.0010.94.293 Time to distant recurrence0.73.0010.84.0220.93.30 15

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22 DDFS by histological grade, ER content, erbB2 protein expression, and erbB2 amplification status. Joensuu H et al. Clin Cancer Res 2003;9:923-930 ©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: ?

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

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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 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 Joyce OShaughnessy, David Miles, Robert Gray, Véronique Diéras, Edith A. Perez, Robin Zon, Javier Cortés, Xian Zhou, See-Chun Phan, Kathy Miller ASCO, 2010

30 30 Overall Survival, Pooled Population Non-BV (n=1008) BV (n=1439) Median, mo26.426.7 HR (95% CI)0.97 (0.86–1.08) 1-yr survival rate (%) 7782

31 31 Analysis of OS by Subgroups

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

33 33 Progression-Free Survival, Pooled Population Non-BV (n=1008) BV (n=1439) Median, mo6.79.2 HR (95% CI)0.64 (0.57–0.71)

34 34 Analysis of PFS by Subgroups

35 35 Méta analyse bévacizumab 1 ère 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 OShaughnessy, 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 Bhattacharya 8 1 Baylor-Sammons Cancer Center, Texas Oncology, U.S. Oncology, Dallas, TX; 2 Institut Curie, Paris, France; 3 UCLA TORI, Los Angeles, CA; 4 University of Pittsburgh, Pittsburgh, PA; 5 Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; 6 Mount Vernon Cancer Centre, London, England; 7 Rydygiera Hospital, Krakow, Poland; 8 BioOncology, Genentech, South San Francisco, CA

37 Overall PFS Results

38 Neoadjuvant or Adjuvant Taxane Treatment

39 Triple Negative

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43 Y A TIL DAUTRES ARGUMENTS CLINIQUES ? Cancers du sein dit « Triple négatif »

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51 ET EN DEHORS DES ESSAIS… DANS LA VRAI VIE… Cancers du sein dit « Triple négatif »

52 ATHENA Efficacité dAvastin / sous groupe TNBC Thomssen et al. SABCS 2009

53 Miles D et al. ESMO 2010

54 Conclusion En attendant les résultats dautres études comportant des thérapies ciblées: – lassociation 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 aujourdhui à nos pratiques les plus courantes

55 Personalizing Cancer Care

56 I Bergman The 7th Seal

57 Thanks The complexity of TNBC treatment strategies


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