Was gynäkologische OnkologInnen über Erblichkeit wissen sollten. 9. Brustkrebskongress Köln und Niederrhein 2016

Transcription

1 Was gynäkologische OnkologInnen über Erblichkeit wissen sollten Rita K. Schmutzler, Universitätsklinik Köln Koordinatorin des Konsortiums Familiärer Brust- und Eierstockkrebs 9. Brustkrebskongress Köln und Niederrhein 2016

2 Neue Daten zur Therapie BRCA1/2- assoziierter Mammakarzinome Ist Platin der neue Standard?

3 Therapy of BRCA1/2-associated Breast Cancer AGO e. V. in der DGGG e.v. sowie in der DKG e.v. Guidelines Breast Version Limited prospective cohort studies with short follow-up time Oxford / AGO LoE / GR Ø Breast conserving therapy: Ø Adequate local tumor control (10 years observation) 2a B + Ø Systemic therapy according to sporadic breast cancer 3a B + Ø BRCA1 mutation status is predictive for chemotherapy response 3b B + Ø Carboplatin (vs. Docetaxel) in MBC 2b a B + Ø PARP inhibitor in breast cancer 2b D +/-* + Overall prognosis has to be considered *Study participation recommended

4

5

6

7 PFS 6,8 PFS 4,8 PFS 3,1 PFS 4,6

8 AGO e. V. in der DGGG e.v. sowie in der DKG e.v. Guidelines Breast Version Early survival analysis of the randomized phase II trial investigating the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2- positive early breast cancer (GeparSixto) Gunter von Minckwitz, Sibylle Loibl, Andreas Schneeweiss, Christoph Salat, Eric Hahnen, Mahdi Rezai, Dirk Michael Zahm, Peter Klare, Jens Uwe Blohmer, Hans Tesch, Fariba Khandan, Peter Fasching, Christian Jackisch, Rita Schmutzler, Valentina Nekljudova, Michael Untch for the GBG/AGO-B study groups

9 San Antonio Breast Cancer Symposium December 8-12, 2015 Design for with TNBC N=315 with centrally confirmed TNBC R ct2, ct3, or ct4a-d or ct1 and cn+ or pn SLN + PM PMCb Surgery Paclitaxel (P) 80 mg/m² q1w Non-pegylated liposomal doxorubicin (M) 20 mg/m² q1w Bevacizumab 15 mg/kg q3w Carbopla@n (Cb) q1w Dose of AUC 2 was reduced to AUC 1.5 aler enrolment of 330 pa@ents von Minckwitz et al. Lancet Oncology 2014 This presenta>on is the intellectual property of GBG and AGO-B. Contact publica>ons@germanbreastgroup.de for permission to reprint and/or distribute.

10 San Antonio Breast Cancer Symposium December 8-12, 2015 pcr Rates by Subtype ypt0 ypn0 HER2-pos. BC TNBC 100% OR 0.84; p= % OR 1.94; p= % 36.8% 32.8% 80% 36.9% 53.2% 60% 60% 40% 40% 20% 20% 0% 0% PM PMCb N=136 N=137 Test for p=0.015 von Minckwitz et al. Lancet Oncology 2014 PM PMCb N=157 N=158 This presenta>on is the intellectual property of GBG and AGO-B. Contact for permission to reprint and/or distribute.

11 San Antonio Breast Cancer Symposium December 8-12, 2015 pcr Rates by gbrca Status and in TNBC ypt0 ypn0 100% 80% gbrca wt OR 2.09 ( ) P=0.005 gbrca mut OR 1.60 ( ) P= % 33.1% 50.8% 50.0% 61.5% 40% 20% 0% PM PM+Cb PM PM+Cb N=121 N=120 N=24 N=26 von Minckwitz G et al., ASCO 2014, updated data; E. Hahnen in prep. This presenta>on is the intellectual property of GBG and AGO-B. Contact publica>ons@germanbreastgroup.de for permission to reprint and/or distribute.

12 San Antonio Breast Cancer Symposium December 8-12, 2015 DFS by gbrca Status and in TNBC Logrank P= This presenta>on is the intellectual property of GBG and AGO-B. Contact for permission to reprint and/or distribute.

13 San Antonio Breast Cancer Symposium December 8-12, 2015 DFS by gbrca Status and pcr in TNBC Logrank P<.0001 This presenta>on is the intellectual property of GBG and AGO-B. Contact for permission to reprint and/or distribute.

14 San Antonio Breast Cancer Symposium - December 08-12, 2015 BRCA mutations, therapy response and prognosis in the neoadjuvant GeparQuinto Study Peter A. Fasching, Sibylle Loibl, Holger Eidtmann, Hans Tesch, Michael Untch, Jörn Hilfrich, Christian Schem, Mahdi Rezai, Bernd Gerber, Serban Dan Costa, Jens-Uwe Blohmer, Tanja Fehm, Jens Huober, Cornelia Liedtke, Volkmar Müller, Valentina Nekljudova, Karsten E Weber, Brigitte Rack, Matthias Rübner, Liewei Wang, James N Ingle, Richard M Weinshilboum, Gunter von Minckwitz and Fergus Couch for the GBG/AGO-B study groups This presentation is the intellectual property of the authors/presenters. Contact them at (publications@germanbreastgroup.de ) for permission to reprint and/or distribute.

15 San Antonio Breast Cancer Symposium - December 08-12, 2015 HER2-negative part of GeparQuinto Core biopsy R EC ECBev * Doc DocBev Surgery (d28-d35 after last Bev infusion) Recruitment of n=1948 HER2 negative patients, N=678 having triple negative tumors. E: Epirubicin 90 mg/m² Doc:Docetaxel 100mg/m² C: Cyclophosphamide 600 mg/m² Bev: Bevacizumab 15 mg/kg (all 3 week cycles) * non responders continued with a prespecified non responder therapy 1 von Minckwitz et al. NEJM, 2012; 2 Gerber et al. Ann Oncol, 2013 This presentation is the intellectual property of the authors/presenters. Contact them at (publications@germanbreastgroup.de ) for permission to reprint and/or distribute.

16 San Antonio Breast Cancer Symposium - December 08-12, 2015 pcr according to treatment and BRCA1/2 pcr (ypt0 ypn0) rate (%) % Patients without BRCA1/2 mutation p= % 38.3% Patients with BRCA1/2 mutation p= % 0 BEV-MUT- BEV+MUT- BEV-MUT+ BEV+MUT+ p (interaction) = Treatment with chemo only Treatment with chemo and BEV This presentation is the intellectual property of the authors/presenters. Contact them at (publications@germanbreastgroup.de ) for permission to reprint and/or distribute.

17 San Antonio Breast Cancer Symposium - December 08-12, 2015 Prognosis according to randomization arm and mutation status Effect of bevacizumab in Mutation Carriers HR = %CI: ) p-value = Test for Interaction: p= Effect of bevacizumab in wildtype Patients HR = %CI: ( ) p-value = This presentation is the intellectual property of the authors/presenters. Contact them at (publications@germanbreastgroup.de ) for permission to reprint and/or distribute.

18 San Antonio Breast Cancer Symposium - December 08-12, 2015 Effect of pcr on prognosis stratified for germline BRCA1/2 mutation status: DFS Effect of pcr in Mutation Carriers HR = %CI: ) p-value = Test for Interaction: p= Effect of pcr in wildtype Patients HR = %CI: ( ) p-value < This presentation is the intellectual property of the authors/presenters. Contact them at (publications@germanbreastgroup.de ) for permission to reprint and/or distribute.

19

20 Therapy of BRCA1/2-associated Breast Cancer proposal 2016 AGO e. V. in der DGGG e.v. sowie in der DKG e.v. Guidelines Breast Version Limited prospective cohort studies with short follow-up time Oxford / AGO LoE / GR Ø Breast conserving therapy: Ø Adequate local tumor control (10 years observation) 2a B + Ø Systemic therapy according to sporadic breast cancer 3a B + Ø BRCA1/2 mutation status is predictive for chemotherapy Response 1b 3b B+ Ø In case of BRCA1 mutation always chemotherapy? Ø Carboplatin (vs. Docetaxel) in MBC 2b a B + Ø PARP inhibitor in breast cancer 2b D +/-* + Overall prognosis has to be considered *Study participation recommended

21 Universität zu Köln Coming soon GBG92 NeoFAM A NEOADJUVANT PHASE II/III RCT FOR BRCA-1/2 ASSOCIATED AND FAMILIAL TRIPLE NEGATIVE BREAST CANCER COMPARING CARBOPLATIN TO PACLITAXEL (NEOFAM) EudraCT no.: DRKS number: Trial protocol code: Uni-Koeln-1722 Heilung durch Innovation, Kompetenz und Partnerschaft

22 Vielen Dank an.. Deutsches Konsor>um ceres cologne center for ethics, rights, economics, and social sciences of health Deutsche Krebshilfe EU Horizon2020