Systemtherapie des primären Mammakarzinoms

Transcription

1 Systemtherapie des primären Mammakarzinoms G. Gitsch E. Stickeler St. Kassian 2016

2 Themenschwerpunkte I Adjuvante Therapie Luminal A Tumoren und CHT Benefit (DBCG77B 25 Jahre Follow-up) HERA (10 Jahre Follow-up) Erweiterte anti-her2 gerichtete Therapie (ExteNET) II Neoadjuvante Therapie Geparsixto Alliance Geparquinto BRCA ADAPT triple-negativ ADAPT triple-positiv

3 Themenschwerpunkte I Adjuvante Therapie Luminal A Tumoren und CHT Benefit (DBCG77B 25 Jahre Follow-up) HERA (10 Jahre Follow-up) Erweiterte anti-her2 gerichtete Therapie (ExteNET)

4 luminal A breast cancer patients derive no benefit from adjuvant chemotherapy: results from DBCG77B randomized trial

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7 San Antonio Breast Cancer Symposium, December 8-12, 2015 HERA TRIAL: 10-Year follow Up of Trastuzumab after Adjuvant Chemotherapy in HER2 Positive Breast Cancer Final Analysis Jackisch C, Piccart M, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, Castro G Jr, Untch M, Smith I, Gianni G, Baselga J, Al-Sakaff N, Lauer S, McFadden E, Leyland-Jones B, Bell R, Dowsett M, Cameron D for the HERA team This presentation is the intellectual property of the presenter. Contact christian.jackisch@sana.de for permission to reprint and/or distribute

8 San Antonio Breast Cancer Symposium, December 8-12, 2015 HERA Trial: 10-Year Follow Up of Trastuzumab after Adjuvant Chemotherapy in HER2 Positive Early Breast Cancer Final Analysis DFS (COMPARISON VS OBSERVATION) Observation only Trastuzumab 1 year Trastuzumab 2 years HERA TRIAL DESIGN ACCRUAL (N=5102) Women with locally determined HER2- positive invasive early breast cancer Surgery + (neo)adjuvant CT ± RT Centrally confirmed IHC 3+ or FISH+ and LVEF 55% Randomization Disease-free survival (%) Pts Events HR (vs observation) 95% CI p-value 2 years ( ) < year ( ) < Observation % 81.3% 75.2% 76.4% 75.9% 70.0% Years from randomization No. remaining Observation only Trastuzumab 1 Year Trastuzumab 2 Years OS (COMPARISON VS OBSERVATION) 71.2% 70.7% 64.7% 69.3% 68.5% 62.5% OBSERVATION n=1698 After ASCO 2005, option of switch to Trastuzumab 1 year Trastuzumab 8 mg/kg 6 mg/kg 3 weekly schedule n= years Trastuzumab 8 mg/kg 6 mg/kg 3 weekly schedule n=1701 CT, chemotherapy; RT, radiotherapy Overall survival (%) Observation only Trastuzumab 1 year Trastuzumab 2 years 94.4% 92.7% 90.7% Pts Events HR (vs observation) 95% CI p-value 2 years ( ) < year ( ) < Observation % 86.9% 84.5% 81.0% 80.7% 75.0% 79.5% 79.4% 72.9% Years from randomization No. at risk Observation only Trastuzumab 1 year Trastuzumab 2 years This presentation is the intellectual property of the presenter. Contact christian.jackisch@sana.de for permission to reprint and/or distribute

9 Probability San Antonio Breast Cancer Symposium, December 8-12, 2015 Probability Cumulative Incidence of Type of DFS Event Hormone Receptor Positive Hormone Receptor Negative Observation only Trastuzumab 1 year Trastuzumab 2 years Solid lines refer to BC events; dashed lines refer to other DFS events Number at risk Years from randomization Observation T 1 Year T 2 Years Number at risk Years from randomization Observation T 1 Year T 2 Years This presentation is the intellectual property of the presenter. Contact christian.jackisch@sana.de for permission to reprint and/or distribute

10 NERATINIB

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12 Safety (Adverse Events 10%) Presented By Shanu Modi at 2015 ASCO Annual Meeting

13 Themenschwerpunkte II Neoadjuvante Therapie Geparsixto Alliance Geparquinto BRCA ADAPT triple-negativ ADAPT triple-positiv

14 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

15 NPLD

16 Geparsixto pcr Raten ypt0 ypn0 TNBC HER2-positive 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% OR 1.94; p= % 58.7% PM PMCb 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 36.8% 32.8% PM n.s. PMCb N=157 N=158 N=136 N=137

17 pcr Rates by gbrca Status and Carboplatin 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.

18 DFS: Effect of Carboplatin in TNBC 3 yrs DFS 85.8% 3 yrs DFS 76.1%

19 DFS by gbrca Status and pcr in TNBC

20 Fazit Geparsixto Signifikant besseres krankheitsfreies Überleben durch Platin bei TNBC (HR=0.56) Vorhersage Heilungsrate durch pcr unabhängig vom BRCA Status Signifikanter Effekt von Carboplatin (pcr and DFS) unabhängig von BRCA Daten sprechen für Einsatz von Carboplatin bei TNBC

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28 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

29 Core biopsy Surgery (d28-d35 after last Bev infusion) HER2-negative part of GeparQuinto EC Doc R ECBev * DocBev 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

30 BRCA1/2 mutations and pcr in all analyzed TNBC patients ypt0 ypn % wildtype P= % BRCA1/2 Mutation TNBC patient population included in both randomization arms Results seem to be consistently similar for BRCA1 and BRCA2 mutation carriers, when analyzed separatly, however sample sizes for this analysis were very small.

31 Effect of germline BRCA1/2 mutation status on prognosis: DFS 100% Survival Probability 90% 80% 70% 60% 50% 40% 30% 20% HR = (95%CI: ) p-value = BRCA1/BRCA2 Mutation Carriers BRCA1/BRCA2 Wildtype Patients 10% 0% Mut Mut DFS, months

32 pcr (ypt0 ypn0) rate (%) pcr according to treatment and BRCA1/ Patients without BRCA1/2 mutation p=0.048 Patients with BRCA1/2 mutation p= % % 35.8% 38.3% BEV-MUT- BEV+MUT- BEV-MUT+ BEV+MUT+ p (interaction) = Treatment with chemo only Treatment with chemo and BEV

33 Fazit BRCA Geparquinto Patientinnen mit BRCA-Mutationen mit höheren pcr-raten Bevacicumab erhöht Effektivität bei TNBC

34 Comparison of 12 weeks neoadjuvant Nab-Paclitaxel combined with Carboplatinum vs. Gemcitabine in triple-negative breast cancer: WSG-ADAPT TN randomized phase II trial Gluz O, Nitz U, Liedtke C, Christgen M, Grischke E, Forstbauer H, Braun M, Warm M, Hackmann J, Uleer C, Aktas B, Schumacher C, Bangemann N, Lindner C, Kümmel S, Clemens M, Potenberg J, Staib P, Kohls A, Sotlar K, Pelz E, Kates RE, Würstlein R, Kreipe H, Harbeck N. on behalf of the ADAPT investigators West German Study Group, Moenchengladbach; Bethesda Hospital, Moenchengladbach; University Hospital Schleswig-Holstein, Camus Lübeck; Institut of Pathology, MHH, Hanover; University Hospital Tübingen, Oncological practice Troisdorf, Clinics Rotkreuz, Munich, Clinics Holweide, Cologne, Marienhospital Witten; Gynecological Practice, Hildesheim, University Hospital, Essen; St. Elisabeth Clinics, Cologne, University Hospital Charite, Berlin, Diakonie Clinics, Hamburg, Cinics Essen-Mitte, Hospital Mutterhaus, Trier; Evangelical Waldkranknehaus, Berlin, St. Antonius Hospital, Eschweiler, Insitite of Pathology, Viersen Ludwig Maximilian University Clincs Munich

35 San Antonio Breast Cancer Symposium, December 8-12, 2015 ADAPT HR-/HER2-: Trial Design Endpoint R EOT Surgery or biopsy* pcr vs. pcr Prognosi s B I O P S Y 3 weeks therapy Efficac y B I O P S Y nab-paclitaxel 125 mg/m 2 Gemcitabine 1000 mg/m 2 Carboplatin AUC2 Standard chemotherapy (4xEC) recommended after surgery / 12-week biopsy (in case of clinical non-pcr) This presentation is the intellectual property of the author. 35 Contact them at oleg.gluz@wsg-online.com for permission to reprint and/or distribute.

36 San Antonio Breast Cancer Symposium, December 8-12, 2015 ADAPT HR-/HER2-: Pathological complete response Hohes Therapieansprechen nach 12 Wochen Therapie Platin/nab-Paclitaxel deutlich Gemzar/nab- Paclitaxel überlegen bei weniger NW This presentation is the intellectual property of the author. 36 Contact them at for permission to reprint and/or distribute.

37 San Antonio Breast Cancer Symposium, December 8-12, 2015 Final analysis of the WSG- ADAPT HER2+/HR+ phase II trial: Efficacy, safety, and predictive markers for 12-weeks of neoadjuvant T-DM1 with or without endocrine therapy vs. trastuzumab+endocrine therapy in HER2- positive hormone-receptor-positive early breast cancer N. Harbeck, O. Gluz, M. Christgen, M. Braun, S. Kuemmel, C. Schumacher, J. Potenberg, S. Kraemer, A. Kleine-Tebbe, D. Augustin, B. Aktas, H. Forstbauer, J. Tio, C. Liedtke, RE Kates, R. Wuerstlein, S. de Haas, A. Kiermaier, HH Kreipe, U. Nitz, on behalf of the West-German Study Group (WSG)-ADAPT investigators

38 San Antonio Breast Cancer Symposium, December 8-12, 2015 ADAPT HER2+/HR+: Trial design 12 Wochen Therapie Endpoint T-DM1 3.6 mg/kg pcr R T-DM1 3.6 mg/kg Endocrine therapy Trastuzumab Endocrine therapy EOT Surgery* vs. pcr vs. pcr *Standard chemotherapy recommended after surgery / 12-week biopsy (in case of clinical non-pcr); trastuzumab to be completed, for a total of one year Hofmann et al, Trials This presentation is the intellectual property of the author. Contact them at nadia.harbeck@med.uni-muenchen.de for permission to reprint and/or distribute.

39 San Antonio Breast Cancer Symposium, December 8-12, 2015 ADAPT HER2+/HR+: pcr (no invasive tumor in breast and nodes) This presentation is the intellectual property of the author. Contact them at for permission to reprint and/or distribute.

40 San Antonio Breast Cancer Symposium, December 8-12, 2015 ADAPT HER2+/HR+: pcr according to menopausal status* *exploratory analysis This presentation is the intellectual property of the author. Contact them at for permission to reprint and/or distribute.

41 Fazit der Autoren 40% pcr nach 12 Wochen Therapie OHNE klassische CHT Wenig Toxizität (kein Haarausfall) Offen: T-DM1 vs. CHT + dualer Blockade (Trast./ Pert.) De-Eskalation möglich

42 Take Home TNBC: Platin sinnvoll, schon Standard? Aktivität von Bevacicumab BRCA Status beeinflusst Outcome wenig HER2 +: Neoadjuvante Therapie De-Eskalation bei best. Subgruppen (HR+) ohne klass. CHT Postneoadjuvante Konzepte

43 GBG 82 - Olympia Olaparib als Post (Neo)-Adjuvante Behandlung bei Patienten mit BRCA Mutation und Hoch-risiko HER2-negativen, primären Mamakarzinom Studiencode: BIG 6-13, NSABP B-55 - Intergruppenstudie AGO-B, GBG und Success -

44 Vielen Dank für Ihre Aufmerksamkeit Februar 2016