The Expert Thoughts. Alessandra Fabi Oncologia Medica 1
|
|
- Eleanore Perkins
- 5 years ago
- Views:
Transcription
1 The Expert Thoughts Alessandra Fabi Oncologia Medica 1
2 My Thoughts Neoadjuvant: from the lessons of the history Adjuvant: Escalation and De-escalation Advanced and HER2+ : field for immunomodulation Brain metastases and outcome: what is changed?
3 Effect of NCT vs ACT on recurrence and mortality EBCTCG Lancet Oncology 2018
4
5 Dual Inhibition in Neoadjuvant Trials Trial Experimental Anti-HER2 pcr with Trastuzumab pcr with Dual inhibition NeoSphere Pertuzumab 29% 46% NeoALTTO Lapatinib 30% 51% CALGB Lapatinib 40% 51%* NSABP B41 # Lapatinib 52% 62%* TRYPHAENA $ Pertuzumab NA 55-64% * Not statistically significant, # Received AC-T, $ No single anti-her2 arm
6 Dual Inhibition in Adjuvant Trials Trial Setting Anti HER2 therapy Primary Endpoint Dual therapy superior to single agents ALTTO adj T T + L T ->L DFS NO APHINITY adj T T + P DFS YES (subtypes*) HR 0.81
7 De-Escalation Strategies in Oncogene Addicted Cancers Minimize chemotherapy Eliminate chemotherapy
8 Neoadjuvant Trials of Dual targeted therapy without chemotherapy Study Phase PT HER2- therapy Endocrine therapy Weeks pcr pcr ER+ pcr ER - TBCRC006 II 64 T+L Yes 12 27% 21% 36% TBCRC023 II 33 T+L Yes 12 15% 9% 20% 61 T+L Yes 24 25% 33% 18% PAMELA II 150 T+L Yes 18 31% 18% 43% NeoSphere II 107 T+P No 16 17% 6% 29%
9 Challenges Predictive Biomarkers for a De-Escalation Approach Mechanisms of Resistance - Dual HER2-targeted therapy with no chemo - Blocking ER in HER2+/ER+ - Novel Anti-HER2 agents - Additional targets/pathways
10 Determinants of Response/Resistance to anti-her2 therapy 1. ER 2. HER2 level (addiction) 3. PI3K pathway deregulation 4. HER2 mutations 5. Microenvironment/immune infiltrate 6. Adaptive or escape pathways: HER3, metabolic (mevalonate), cell cycle
11 2017
12 Are HER2+/ER+ the same tumors? - We may overtreat a subgroup of ER+, HER+ BC in the (neo)-adjuv (enough anti HER2+OT??) - This subgroup may suffer late recurrence (similar to what we see with some HER2-/ER+ cancers) - Can we identify this subgroup drived by ER?
13 2017
14 SABC intrinsic subtype differed between HR- and HR+
15 TBCRC 006 (HELP Study) Stage II/III HER2+ Breast CA N=64 LAPATINIB + TRASTUZUMAB +/- LETROZOLE Wee k 1 W 2 W 3 Biopsy W 4 W 5 W 6 W 7 W 8 W 9 Biopsy W 1 0 W 1 1 W 12 Biopsy Baseline Biopsy PTEN IHC PIK3CA mutations M Rimawi, JCO 2013
16 Correlation with pcr pcr No pcr Marker n % n % P PTEN (n=59) 0.04 High ( 100) Low (<100) PIK3CA (n=46) 0.14 Wild type Mutation PTEN low or PIK3CA mutation (n=43) No Yes There was no correlation between PIK3CA mutation status, PTEN level, and ER.
17 Neoadjuvant therapy in HER2+ EBC LESSONS LEARNED FROM NEOADJUVANT TRIALS I. First generation Trastuzumab + chemo > chemo alone
18 Trastuzumab and chemotherapy Trastuzumab + chemotherapy Chemotherapy alone MD Anderson 1 H+(T FEC) T FEC n=45 n= P=NR NOAH 2 H+(AT T CMF) AT T CMF n=117 n= P< pcr (%) No evidence of residual invasive cancer, both in breast and axilla No evidence of residual disease in breast tissue pcr, pathological complete response; H, trastuzumab; T, taxane FEC, 5-fluorouracil+epirubicin+cyclophosphamide; AT, doxorubicin+paclitaxel CMF, cyclophosphamide+methotrexate+5-fluorouracil; EC, epirubicin+cyclophosphamide 1. Buzdar AU, et al. 2007,2. Gianni L, et al. 2010
19 Improved pcr rate translates into improved outcome with Trastuzumab 5-year event-free survival 5-year overall survival *EFS, Event free survival; HR, Hazard ratio; OS, Overall survival. Gianni L, et al. 2014
20 Dual HER2 blockade LESSONS LEARNED FROM NEOADJUVANT TRIALS II. Second generation Dual HER2 blockade + chemo > single HER2 blockade + chemo
21 pcr, % 95% CI pcr, % 95% CI Pertuzumab and trastuzumab TH (n=107) docetaxel ( mg/m 2 ) trastuzumab (8 6 mg/kg) THP (n=107) docetaxel ( mg/m 2 ) trastuzumab (8 6 mg/kg) pertuzumab ( mg) HP (n=107) trastuzumab (8 6 mg/kg) pertuzumab ( mg) TP (n=96) docetaxel ( mg/m 2 ) pertuzumab ( mg) Study dosing: q3w x 4 Gianni L, et al. Lancet Oncol 2011 S U R G E R Y T H TH P H P 24 TP ER or PR positive ER and PR negative TH THP HP TP 6
22 Beyond dual blockade LESSONS LEARNED FROM NEOADJUVANT TRIALS III. Third generation Identify the subset which can benefit from a chemo-sparing regimen
23 HER2+ /HR- disease % PCR rates % Dual HER2 blockade alone 62% Dual HER2 blockade + taxane 73-80% Dual HER2 blockade + taxane + other agent (anthrac., carbo) Who are these patients with HER2+ HR- disease who perhaps do not need chemo? Based on NeoSphere, NeoAltto, Tryphaena
24 HER2+ /HR- disease PIK3CA mutations/ PTEN loss Improved tailoring? TIL s Immune signatures
25 ADAPT study in HER2+/HR+ International, prospective, randomized phase II trial Wk 12 Pts with ER+ and/or PgR+, HER2+, ct1c - ct4a-c, cn, cm0 BC and adequate organ function, LVEF 50%, normal ECG (N = 375) T-DM1 3.6 mg/kg Q3W (n = 119) T-DM1 3.6 mg/kg Q3W + ET* (n = 127) Trastuzumab 8 mg/kg loading dose, then 6 mg/kg Q3W + ET* (n = 129) Surgery *Tamoxifen if premenopausal; aromatase inhibitor (of investigator s choice) if postmenopausal. Standard chemotherapy (1-yr trastuzumab) recommended after surgery or 12-wk biopsy (if clinical non-pcr). Primary endpoint: pcr (no invasive carcinoma in breast/nodes) Secondary endpoints: dynamic testing evaluation, EFS, OS, safety 1. Harbeck N, et al. SABCS Abstract S Hofmann D, et al. Trials. 2013;14:261.
26 ADAPT Trial Outcome, n/n (%) T-DM1 T-DM1 + ET pcr (ypt0 or ypt0/is, ypn0) All pts* Premenopausal women Postmenopausal women 48/117 (41.0) 22/58 (37.9) 26/59 (44.1) *P <.001 for comparison between each T-DM1 arm vs trastuzumab + ET. Low cellularity (< 500 tumor cells) or Ki67 decline 30%in 3-wk biopsy. Harbeck N, et al. SABCS Abstract S /123 (41.5) 24/63 (38.1) 27/60 (45.0) Trastuzumab + ET 18/119 (15.1) 8/59 (13.6) 10/60 (16.7) Near pcr (ypt1a) 14/117 (12.0) 14/123 (11.4) 5/119 (4.2) Early response Nonresponders Responders 9/36 (25.0) 24/61 (39.3) 6/25 (24.0) 36/76 (47.4) 5/40 (12.5) 11/62 (17.7)
27 Adjuvant therapy in HER2 positive EBC Optimal Adjuvant Therapy in 2018 for the average patient with HER2-positive breast cancer
28 Long-term DFS benefit with adjuvant Trastuzumab for 1 year Study HERA 1 4 CT+/-RT H vs. CT+/-RT BCIRG AC TH H vs. AC T TCH vs. AC T Combined analysis 6-8 (NCCTG N9831/ NSABP B-31) AC TH H vs. AC T HR, hazard ratio Follow-up (years) N Piccart-Gebhart MJ, et al. 2005; 2. Smith I, et al. 2007; 3. Gianni L, et al. 2011, 4. Goldhirsch A, et al Slamon D, et al. 2011; 6. Romond EH, et al. 2005; 7. Perez EA, et al. 2011; 8. Perez EA, et al HR Favours 1 Favours 2 Trastuzumab HR (95% CI) observation
29 Escalation: where do we start from? 1. Longer trastuzumab duration (Hera 2y arm ) 2. Adding bevacizumab to trastuzumab (Beth ) 3. Dual HER2 blockade - Lapatinib + trastuzumab (ALTTO) - Pertuzumab + trastuzumab (APHINITY ) 4. T-DM1 after neoadjuvant CT + trastuzumab in case of residual disease (Katherine?) 5. Extended neratinib ( )
30 Extended Neratinib HER2+ Stage II-IIIC node positive BC following CT + 12 months of trastuzumab (adj) (N=2821) R Neratinib 240 mg orally daily for 1 year Placebo Orally daily for 1 year DFS DFS CT, chemotherapy; adj, adjuvant; DFS, disease-free survival; BC, breast cancer. Press release - Puma Biotechnology July 22nd, 2014 Extended DFS by 33% compared with placebo (HR = 0.67; P =.0046) Martin et al Lancet 2017
31 ITT ER+ Impact of Hormonal Therapy? HER2+/HT+ different tumors? ER-
32 Katherine Neoadjuvant CT + trastuzumab Residual invasive cancer R T-DM1 Trastuzumab Primary endpoint : IDFS 900/1400 patients recruited as of today
33 KAITLIN HER2+ Node+ or Node-, ERand T>2cm R AC x 4 or FEC x3 AC x 4 or FEC x3 TAXANE TRASTUZUMAB PERTUZUMAB T-DM1 PERTUZUMAB IDFS HO 89,5% 93,1% 1300/2500 women recruited Worrysome : taxane + trastuzumab = T-DM1 = T-DM1 + pertuzumab in the first line metastatic MARIANNE trial! 35
34 SABCS 5 studies
35 SABC STANDARD TREATMENT: TRASUZUMAB FOR 1 YR Sold SABCS 2017 SABCS 2017 SABCS
36 De-Escalation treatment in HER2+: from where? 1. Tumor size 2. Age 3. Response to preoperative therapy
37 Point 1 APT Trial HER2+ Node Negative < 3 cm N=406 Enroll P P P P P P P P P P P P T T T T T T T T T T T T PACLITAXEL 80 mg/m 2 + TRASTUZUMAB 2 mg/kg x 12 T T T T T T T T T T T T T 3-year DFS 95% Conf. Interval 98.7% 97.6% to 99.8% Poisson p-value: < FOLLOWED BY 13 EVERY 3 WEEK DOSES OF TRASTUZUMAB (6 mg/kg) Tolaney et al, NEJM 2015
38 SABCS SABCS 2017 SABCS 2017
39 ATEMPT trial (randomized phase II) T-DM1 Stage I R(3:1) Trastuzumab + Paclitaxel Objectives: Primary DFS Secondary Outcome Measures :DFS in Patient Groups Defined by Tumor Size < 1cm or >/= 1 cm and HR Percentage of participants with Grade 3-4 Cardiac Dysfunction Recruitment ongoing from 2013
40 Point 2 age > 60 yrs stage I III HER2+ Age and adj therapy ATOP trial (phase II) T-DM1 for 1 yr age RESPECT trial (randomized phase II) Trastuzumab alone stage I IIIA HER2+ Recruitment ongoing Trastuzumab plus chemotherapy.
41 Question: EC/taxane + trastuzumab and pertuzumab vs with a taxane + trastuzumab and pertuzumab? Point 3 We consider using escalation of biologic therapy as a mechanism to de-escalate chemotherapy. If adding pertuzumab to trastuzumab-based chemotherapy is found to improve long-term outcomes in the APHINITY trial, perhaps patients may achieve similar outcomes with less chemotherapy and highly effective biologic therapy
42 MY TOUGHTS Escalation attempts : preliminary conclusions Failed X X X Trastuzumab x 2y Trastuzumab + bevacizumab Trastuzumab + lapatinib Trastuzumab followed by neratinib Succeeded? Trastuzumab + pertuzumab?? T-DM1 after neoadj CT + trast? X
43 MY THOUGHTS De-Escalation attempts : preliminary conclusions Failed Succeeded X(so far ) Shorten trastuzumab duration Eliminate the anthracycline component? Use T-DM1 + pertuzumab instead of taxane + trastuzumab + pertuzumab? Use of only trastuzumab without CT in stage I older pts X (in selected pts!)??
44 METASTATIC DISEASE
45 HER2+ Disease TILs come to stage HER2 + no longer the only prognostic factor of disease and predictive of response TILs associated with improved prognosis among patients with HER2-positive breast cancer The TIL count predicts a pathologic complete response to neoadjuvant chemotherapy, trastuzumab, and lapatinib Increased TIL count predicted better distant DFS in HER2+ early BC pts (FinHER, NeoALTTO) higher TIL values are significantly associated with improved overall survival, suggesting that the effect of antitumour immunity extends to the advanced setting (Cleopatra data) Ali HR, Ann Oncol 2014; Bianchini G, Lancet Oncol 2014; Denkert C, J Clin Oncol 2010; Dieci MV et al, Ann Oncol 2015; Denkert C, J Clin Omncol 2015; Loi S, Ann Oncol 2014,
46 Stromal TILs and Survival in HER2+ Further clinical studies in this cancer subtype should consider TILs as a stratification factor Luen, Lancet Oncol 2016
47 Postulated mechanism of engagement of the innate and adaptive immune system through HER2-targeted monoclonal antibodies CTL ADCC IFNγ Tumor NK Coated monoclonal antibodies have demonstrated debris Tumor cell to generate an in vivo vaccine-like effect IFNγ Phagocytosis IL-2 death (immunogenic or not immunogenic) NK/DC crosstalk Debris or dying cells DC Cross presentation Trastuzumab, rituximab and others CTL CD4 Th1 Legend Tumor cell NK cell Cytotoxic T-cell Activated Cytotoxic T-cell CD4 (Th1) Dendritic cells MHC I MHC II TCR HER2 FcγR Trastuzumab/pertuzumab Bianchini G & Gianni L. Lancet Oncol 2014
48 HER2 targeted monoclonals combinations
49 Preclinical studies are supportive of benefit for combining anti- HER2 antibodies and immune checkpoints inhibitors Anti-HER2 mab and Anti-PD1 TDM1 and Anti-PD1/Abti-CTLA4 Stagg J et al PNAS 2011 Muller P et al Sci Transl Med 2015
50 Panacea Study SABCS 2017 CS 2017 Loi 2017
51 017 Loi 2017
52 Immunotherapy excitement in breast cancer Trial ongoing with immunechekpoint inhibitors trials 38 TNBC (only) 12 ER+/HER2- (only) 6 HER2+ (only) 10 trials trials of combinations Only breast cancer Multiple solid Phase I or II Phase III Marketed ClinicalTrialsGov (updated )
53 who survives longer with brain metastases? Martin, Jama 2017
54 HER2+ population
55 Survival Mounsey, Clin Breast Cancer 2017
56 The HERBA trial a retrospective study on pts with HER2+ BC and brain metastases 154 HER2+ve BC pts diagnosed with BMs from January 2005 to December 2014 Median OS from the diagnosis of BMs was 24.5 months, with no significant difference between pts diagnosed in period (25.2 months) and those diagnosed in period (21.5 months; p=0.42). No significant difference in terms of mos between pts with and those without previously diagnosed systemic metastases (23 vs 27 months; p=0.469) and this data suggest that the occurrence of BMs is a predominant prognostic factor for HER2+ve BC pts Gori et al. 2017
57 Grazie
(Neo)Adjuvant Chemotherapy and biological Agents (essentials in HER2 and TN early breast cancer)
(Neo)Adjuvant Chemotherapy and biological Agents (essentials in HER2 and TN early breast cancer) Giuseppe Curigliano MD, PhD Breast Cancer Program Division of Experimental Therapeutics Outline Neoadjuvant
More informationTarget biologico e meccanismo d azione dei farmaci anti-her2: il continuum dal setting Neoadiuvante alla malattia metastatica
Target biologico e meccanismo d azione dei farmaci anti-her2: il continuum dal setting Neoadiuvante alla malattia metastatica Giuseppe Curigliano MD, PhD Breast Cancer Program Division of Experimental
More informationBiomarkers for HER2-directed Therapies : Past Failures and Future Perspectives
Biomarkers for HER2-directed Therapies : Past Failures and Future Perspectives Ian Krop Dana-Farber Cancer Institute Harvard Medical School Inchon 2018 Adjuvant Trastuzumab Improves Outcomes in HER2+ Breast
More informationNovel Preoperative Therapies for HER2-Positive Breast Cancer. Debu Tripathy, MD University of Southern California Norris Comprehensive Cancer Center
Novel Preoperative Therapies for HER2-Positive Breast Cancer Debu Tripathy, MD University of Southern California Norris Comprehensive Cancer Center Key Findings to Date in the Neoadjuvant Therapy of HER2+
More information(Neo-) Adjuvant chemotherapy and biological agents. Giuseppe Curigliano MD, PhD University of Milano and European Institute of Oncology
(Neo-) Adjuvant chemotherapy and biological agents Giuseppe Curigliano MD, PhD University of Milano and European Institute of Oncology Outline Neoadjuvant treatment in triple negative and HER2 positive
More information(NEO-)ADJUVANT THERAPY FOR HER-2+ EBC
(NEO-)ADJUVANT THERAPY FOR HER-2+ EBC Rebecca Dent, MD FRCP (Canada) Senior Consultant, National Cancer Center Singapore Associate Professor, Duke-NUS www.abc-lisbon.org When to question a pathology report?
More information(Neo) Adjuvant systemic therapy for HER-2+ EBC
(Neo) Adjuvant systemic therapy for HER-2+ EBC F. Cardoso, MD Director, Breast Unit, Champalimaud Clinical Center, Lisbon, Portugal ESMO Board of Directors & NR Committee Chair ESO Breast Cancer Program
More informationThe Role of Pathologic Complete Response (pcr) as a Surrogate Marker for Outcomes in Breast Cancer: Where Are We Now?
1 The Role of Pathologic Complete Response (pcr) as a Surrogate Marker for Outcomes in Breast Cancer: Where Are We Now? Terry Mamounas, M.D., M.P.H., F.A.C.S. Medical Director, Comprehensive Breast Program
More informationPositive HER-2 tumor. How to incorporate the new drugs into neoadjuvance
Oncology Department Vall d Hebron University Hospital Barcelona. Spain Positive HER-2 tumor. How to incorporate the new drugs into neoadjuvance Javier Cortés June/2013 MD Anderson experience Buzdar et
More informationNeo-adjuvant and adjuvant treatment for HER-2+ breast cancer
Neo-adjuvant and adjuvant treatment for HER-2+ breast cancer Angelo Di Leo «Sandro Pitigliani» Medical Oncology Unit Hospital of Prato Istituto Toscano Tumori Prato, Italy NOAH: Phase III, Open-Label Trial
More informationSystemic Therapy of HER2-positive Breast Cancer
Systemic Therapy of HER2-positive Breast Cancer Tanja Cufer, MD, PhD University Clinic Golnik, Medical Faculty Ljubljana, Slovenia ESO ESMO Masterclass, Belgrade 2017 Relative Risk HER2-positive Breast
More informationSystemic therapy: HER-2 update. Hans Wildiers Multidisciplinair Borst Centrum/Algemene medische oncologie UZ Leuven
Systemic therapy: HER-2 update Hans Wildiers Multidisciplinair Borst Centrum/Algemene medische oncologie UZ Leuven New drugs Strategic issues Specific anti-her2 drugs Lapa$nib /Nera$nib Baselga & Swain,
More informationOptimizing anti-her-2 therapies for ABC Potential role of immunotherapy. Javier Cortes, Ramon y
Optimizing anti-her-2 therapies for ABC Potential role of immunotherapy Javier Cortes, Ramon y Cajal University Hospital, Madrid, Spain Vall d Hebron Institute of Oncology (VHIO), Medica Scientia Innovation
More informationSystemic Therapy of HER2-positive Breast Cancer
Systemic Therapy of HER2-positive Breast Cancer Tanja Cufer, MD, PhD University Clinic Golnik, Medical Faculty Ljubljana, Slovenia ESO ESMO Masterclass, Belgrade 2018 HER2-positive Breast Cancer Adjuvant
More informationReview of adjuvant and neo-adjuvant abstracts from SABCS 2011 January 7 th 2012
Review of adjuvant and neo-adjuvant abstracts from SABCS 2011 January 7 th 2012 Ruth M. O Regan, MD Professor and Vice-Chair for Educational Affairs, Department of Hematology and Medical Oncology, Emory
More informationTreatment of Early-Stage HER2+ Breast Cancer
Treatment of Early-Stage HER2+ Breast Cancer Chau T. Dang, MD Chief, MSK Westchester Medical Oncology Service Breast Medicine Service Memorial Sloan Kettering Cancer Center Disclosures I have research
More informationPRO: Pathologic Complete Response Does Predict Outcome for Early Stage Breast Cancer Patients
PRO: Pathologic Complete Response Does Predict Outcome for Early Stage Breast Cancer Patients Amelia B. Zelnak, M.D., M.Sc. Assistant Professor of Hematology and Medical Oncology Winship Cancer Institute
More informationTreatment of Early Stage HER2-positive Breast Cancer (One size does not fit all)
Treatment of Early Stage HER2-positive Breast Cancer (One size does not fit all) 8 November 2014 Edward H. Romond, M.D. Professor of Medicine Lucille Parker Markey Cancer Center University of Kentucky
More informationExiste-t-il un sous groupe à risque qui pourrait bénéficier d une modification de la durée de traitement par trastuzumab? X. Pivot CHRU De Besançon
Existe-t-il un sous groupe à risque qui pourrait bénéficier d une modification de la durée de traitement par trastuzumab? X. Pivot CHRU De Besançon In 25 results of 4 Adjuvant Herceptin trials have definitively
More informationLocally Advanced Breast Cancer: Systemic and Local Therapy
Locally Advanced Breast Cancer: Systemic and Local Therapy Joseph A. Sparano, MD Professor of Medicine & Women s Health Albert Einstein College of Medicine Associate Chairman, Department of Oncology Montefiore
More informationCáncer de mama HER2+/RE+ vs HER2+/RE : Una misma enfermedad? Dra E. Ciruelos Departamento de Oncología Médica Hospital Universitario 12 de Octubre
Cáncer de mama HER2+/RE+ vs HER2+/RE : Una misma enfermedad? Dra E. Ciruelos Departamento de Oncología Médica Hospital Universitario 12 de Octubre Recurrence of HER2-positive breast cancer (A) Time to
More informationThe next wave of successful drug therapy strategies in HER2-positive breast cancer. Hans Wildiers University Hospitals Leuven Belgium
The next wave of successful drug therapy strategies in HER2-positive breast cancer Hans Wildiers University Hospitals Leuven Belgium Trastuzumab in 1st Line significantly improved the prognosis of HER2-positive
More informationNovità e sequenze terapeutiche nel carcinoma mammario HER2 positivo Terapia neoadiuvante Claudio Zamagni
Novità e sequenze terapeutiche nel carcinoma mammario HER2 positivo Terapia neoadiuvante Claudio Zamagni Direttore SSD Oncologia Medica Addarii Policlinico S.Orsola-Malpighi Bologna Open questions in HER2+
More informationUpdate in the treatment of Her2- overexpressing breast cancers. Fabrice ANDRE Institut Gustave Roussy Villejuif, France
Update in the treatment of Her2- overexpressing breast cancers Fabrice ANDRE Institut Gustave Roussy Villejuif, France Questions Should tumors
More informationNovel Preoperative Therapies for HER2-Positive Breast Cancer
Key Findings to Date in the Neoadjuvant Therapy of H2+ Breast Cancer Novel Preoperative Therapies for H2-Positive Breast Cancer Debu Tripathy, MD University of Southern California Norris Comprehensive
More informationSystemic Therapy Considerations in Inflammatory Breast Cancer
Systemic Therapy Considerations in Inflammatory Breast Cancer Shani Paluch-Shimon, MBBS, MSc Director, Breast Oncology Unit Shaare Zedek Medical Centre, Jerusalem Israel Disclosures Roche: Speakers bureau,
More informationTreatment of Early Stage HER2-positive Breast Cancer
Treatment of Early Stage HER2-positive Breast Cancer 3 November 2012 Edward H. Romond, M.D. Professor of Medicine Lucille Parker Markey Cancer Center University of Kentucky Lexington, KY Molecular Portrait
More informationCurrent and Future perspectives of HER2+ BC
2018.4.6 GBCC Satellite symposium Current and Future perspectives of HER2+ BC Jee Hyun Kim, M.D., Ph.D. Seoul National University Bundang Hospital Seoul National University College of Medicine Disclaimer
More informationXII Michelangelo Foundation Seminar
XII Michelangelo Foundation Seminar The opportunity of the neoadjuvant approach L. Gianni, Milan, I XII Michelangelo Foundation Seminar Milano, October 12, 2012 The opportunity of the neoadjuvant approach
More informationSustained benefits for women with HER2-positive early breast cancer JORGE MADRID BIG GOCCHI PROTOCOLO HERA
Sustained benefits for women with HER2-positive early breast cancer JORGE MADRID BIG GOCCHI PROTOCOLO HERA The fascinating history of Herceptin 1981 1985 1987 1990 1992 1998 2000 2005 2006 2008 2011 Murine
More informationAny News in EBC? Ann H. Partridge, MD, MPH Dana-Farber Cancer Institute November 11, 2016
Any News in EBC? Ann H. Partridge, MD, MPH Dana-Farber Cancer Institute November 11, 2016 Yes! Age disparities vary by tumor subtype Genomic risk prediction data in young women Adjuvant systemic therapy
More informationMalattia HER-2 positiva
Novità sul trattamento del carcinoma mammario Malattia HER-2 positiva Patrizia Vici Neoadjuvant - Adjuvant - Advanced Prognostic/Predictive factors..her-2 heterogeneity.. Neoadjuvant Phase II Pre-planned
More informationHER2-Targeted Rx. An Historical Perspective
HER2-Targeted Rx An Historical Perspective Trastuzumab: Front Line Rx for MBC Median 20.3 v. 25.1 mo P = 0.046 HR 0.8 65% of control patients crossed over Slamon D, et al. N Engl J Med, 2001; 344:783 Trastuzumab:Front-line
More informationNeoadjuvantTreatment In BC When, How, Who?
NeoadjuvantTreatment In BC When, How, Who? Clifford Hudis, M.D. Chief, Breast Cancer Medicine Service, MSKCC Professor of Medicine, Weill Cornell Medical College President, ASCO 15 Potential Benefits Of
More informationNon-Anthracycline Adjuvant Therapy: When to Use?
Northwestern University Feinberg School of Medicine Non-Anthracycline Adjuvant Therapy: When to Use? William J. Gradishar MD Betsy Bramsen Professor of Breast Oncology Director, Maggie Daley Center for
More information2014 San Antonio Breast Cancer Symposium Review
2014 San Antonio Breast Cancer Symposium Review HER2 Positive Disease 01-10-2015 Elisavet Paplomata, MD Assistant Professor Hematology & Medical Oncology Emory University Winship Cancer Institute S6-01
More informationXII Michelangelo Foundation Seminar
XII Michelangelo Foundation Seminar Paradigm shift? The Food and Drug Administration collaborative project P. Cortazar, Silver Spring, USA FDA Perspective: Moving from Adjuvant to Neoadjuvant Trials in
More informationTriple Negative Breast cancer New treatment options arenowhere?
Triple Negative Breast cancer New treatment options arenowhere? Ofer Rotem, M.D., B.Sc. Breast Unit, Davidoff center Rabin Medical center October 2017 Case 6/2013 - M.D., 38 years old woman, healthy, no
More informationBiomarker research in HER2 positive breast cancer : a journey into the desert
WIN 9th Symposium 2017 Expediting Global Innovation in Precision Cancer Medicine Paris, June 26 & 27, 2017 Biomarker research in HER2 positive breast cancer : a journey into the desert Martine J. Piccart-Gebhart,
More informationAdvances in Breast Cancer Therapeutics in the Adjuvant and Metastatic Settings. Eve Rodler, MD University of California at Davis October 2016
Advances in Breast Cancer Therapeutics in the Adjuvant and Metastatic Settings Eve Rodler, MD University of California at Davis October 2016 17th Annual Advances in Oncology September 30-October 1, 2016
More informationTriple negative breast cancer -neoadjuvant and adjuvant systemic therapy
Triple negative breast cancer -neoadjuvant and adjuvant systemic therapy Sung-Bae Kim, MD, PhD Department of Oncology Asan Medical Center University of Ulsan College of Medicine Seoul, Korea DISCLOSURE
More informationIntroduction. Approximately 20% of invasive breast cancers
Introduction Approximately 2% of invasive breast cancers overexpress HER2 The current standard of care for neoadjuvant therapy is dual-targeted therapy with trastuzumab and pertuzumab plus chemotherapy
More informationASCO 2017 BREAST CANCER HIGHLIGHTS
Post-ASCO 24 th June 2017, Dolce La Hulpe, Belgium ASCO 2017 BREAST CANCER HIGHLIGHTS Martine J. Piccart-Gebhart, MD, PhD Jules Bordet Institute, Brussels, Belgium Université Libre de Bruxelles Breast
More informationAdjuvant Chemotherapy TNBC & HER2 Subtype
Adjuvant Chemotherapy TNBC & HER2 Subtype 2015.08.15 Gun Min Kim Yonsei Cancer Center Division of Medical Oncology Department of Internal Medicine Yonsei University College of Medicine gmkim77@yuhs.ac
More informationLecture 5. Primary systemic therapy: clinical and biological endpoints
Lecture 5 Primary systemic therapy: clinical and biological endpoints Valentina Guarneri, M.D., Ph.D. Primary systemic therapy in breast cancer Firstly introduced d into clinical i l practice in 70s for
More informationUpdate HER2. Rupert Bartsch. Department of Medicine 1, Clinical Division of Oncology Comprehensive Cancer Center Vienna Medical University of Vienna
Update HER2 Rupert Bartsch Department of Medicine 1, Clinical Division of Oncology Comprehensive Cancer Center Vienna Medical University of Vienna HER2: A Unique Story of Success Analysis of outcome in
More informationBREAST CANCER RISK REDUCTION (PREVENTION)
BREAST CANCER RISK REDUCTION (PREVENTION) Articles Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled
More informationNadia Harbeck Breast Center University of Cologne, Germany
Evidence in Favor of Taxane Based Combinations and No Anthracycline in Adjuvant and Metastatic Settings Nadia Harbeck Breast Center University of Cologne, Germany Evidence in Favor of Taxane Based Combinations
More informationWhat to do after pcr in different subtypes?
What to do after pcr in different subtypes? Luca Moscetti Breast Unit Università degli Studi di Modena e Reggio Emilia Policlinico di Modena, Italy Aims of neoadjuvant therapy in breast cancer Primary
More informationShould pertuzumab be used as part of neoadjuvant treatment prior to the release of the APHINITY trial results?
Commentary Should pertuzumab be used as part of neoadjuvant treatment prior to the release of the APHINITY trial results? Tom Wei-Wu Chen 1, Ching-Hung Lin 1,2, Chiun-Sheng Huang 3 1 Department of Oncology,
More informationBreast Cancer Earlier Disease. Stefan Aebi Luzerner Kantonsspital
Breast Cancer Earlier Disease Stefan Aebi Luzerner Kantonsspital stefan.aebi@onkologie.ch Switzerland Breast Cancer Earlier Disease Diagnosis and Prognosis Local Therapy Surgery Radiation therapy Adjuvant
More informationDennis J Slamon, MD, PhD
I N T E R V I E W Dennis J Slamon, MD, PhD Dr Slamon is Professor of Medicine, Chief of the Division of Hematology/Oncology and Director of Clinical and Translational Research at UCLA s David Geffen School
More informationA vision for HER2 future
School of Medical Oncology Department of Medical and Biological Sciences - University of Udine Department of Oncology - University Hospital of Udine A vision for HER2 future Current therapeutic algorithm
More informationEnfermedad con sobreexpresión de HER-2 neu
Enfermedad con sobreexpresión de HER-2 neu Elsa Dalmau Parc Taulí Sabadell. Hospital Universitari. Enfermedad con sobreexpresión de HER-2 neu ÍNDICE Neoadyuvancia Adyuvancia Enfermedad avanzada Enfermedad
More informationSt Gallen 2017 controversies & consensus
St Gallen 2017 controversies & consensus Shani Paluch-Shimon, MBBS, MSc Head, Breast Cancer Service for Young Women Breast Unit, Division of Oncology Sheba Medical Centre June 2017 St Gallen 2017 De-escalation
More informationpan-canadian Oncology Drug Review Initial Clinical Guidance Report Pertuzumab (Perjeta) Neoadjuvant Breast Cancer April 30, 2015
pan-canadian Oncology Drug Review Initial Clinical Guidance Report Pertuzumab (Perjeta) Neoadjuvant Breast Cancer April 30, 2015 DISCLAIMER Not a Substitute for Professional Advice This report is primarily
More informationHER2-positive Breast Cancer
HER2-positive Breast Cancer Multiple choices what to use when? Thomas Ruhstaller Brustzentrum St. Gallen Adjuvant setting NCIC MA5 N Engl J Med 06, 2103 6 x CEF can 6 x CMF oral HER2 + pg schlecht in allen
More informationRadiotherapy Management of Breast Cancer Treated with Neoadjuvant Chemotherapy. Julia White MD Professor, Radiation Oncology
Radiotherapy Management of Breast Cancer Treated with Neoadjuvant Chemotherapy Julia White MD Professor, Radiation Oncology Agenda Efficacy of radiotherapy in the management of breast cancer in the Adjuvant
More informationUpdate on the Management of HER2+ Breast Cancer. Christian Jackisch, MD, PhD Sana Klinikum Offenbach Offenbach, Germany
Update on the Management of HER2+ Breast Cancer Christian Jackisch, MD, PhD Sana Klinikum Offenbach Offenbach, Germany Outline Treatment strategies for HER2-positive metastatic breast cancer since First
More informationBreast Cancer: ASCO Poster Review
Breast Cancer: ASCO Poster Review Carmen Criscitiello, MD, PhD Istituto Europeo di Oncologia Milano HER2+ SUBTYPE Research questions in early HER2+ BC De-escalation of toxicity without compromising efficacy
More informationLo Studio Geparsepto. Alessandra Fabi Oncologia Medica 1
Lo Studio Geparsepto Alessandra Fabi Oncologia Medica 1 nab-paclitaxel Versus Solvent-Based Paclitaxel in Neoadjuvant Chemotherapy for Early Breast Cancer (GeparSepto GBG 69): A Randomised, Phase III Trial
More informationTNBC: What s new Déjà vu All Over Again? Lucy R. Langer, MD MSHS Compass Oncology - SABCS 2016 Review February 21, 2017
TNBC: What s new Déjà vu All Over Again? Lucy R. Langer, MD MSHS Compass Oncology - SABCS 2016 Review February 21, 2017 The problem with TNBC 1. Generally more aggressive 2. ONLY chemotherapy 3. No other
More informationPROGNOSTICO DE PACIENTES COM CA DE MAMA METASTATICO HER2+: PODEMOS FAZER MAIS? TDM-1 AND BEYOND!
II Simpósio Internacional de Câncer de Mama para o Oncologista Clínico PROGNOSTICO DE PACIENTES COM CA DE MAMA METASTATICO HER2+: PODEMOS FAZER MAIS? TDM-1 AND BEYOND! INGRID A. MAYER, MD, MSCI Assistant
More informationSesiones interhospitalarias de cáncer de mama. Revisión bibliográfica 4º trimestre 2015
Sesiones interhospitalarias de cáncer de mama Revisión bibliográfica 4º trimestre 2015 Selected papers Prospective Validation of a 21-Gene Expression Assay in Breast Cancer TAILORx. NEJM 2015 OS for fulvestrant
More informationDR. BOMAN N. DHABHAR Consulting Oncologist Jaslok Hospital, Fortis Hospital Mulund, Wockhardt Hospital Mumbai & BND Onco Centre INDIA
Recent Advances of Docetaxel in Management of Breast Cancer DR. BOMAN N. DHABHAR Consulting Oncologist Jaslok Hospital, Fortis Hospital Mulund, Wockhardt Hospital Mumbai & BND Onco Centre INDIA 1 ADJUVANT
More informationHighlights. Padova,
Highlights P Pronzato Padova, 17.11.2012 Last 12 Months Main Meetings SABCS 2011 (San Antonio) EBCC 8 2012 (Wien) ASCO 2012 (Chicago) ESMO/ECCO 2012 (Wien) The Medical Oncology Job Risk Manager Strategy
More informationEARLY BREAST CANCER, HER2-POSITIVE
EARLY BREAST CANCER, HER2-POSITIVE CLINICAL CASE DISCUSSION Elżbieta Senkus Medical University of Gdańsk Gdańsk, Poland esmo.org DISCLOSURES Honoraria: Amgen, Astellas, AstraZeneca, Bayer, BMS, Celgene,
More informationTriple Negative Breast Cancer: Part 2 A Medical Update
Triple Negative Breast Cancer: Part 2 A Medical Update April 29, 2015 Tiffany A. Traina, MD Breast Medicine Service Memorial Sloan Kettering Cancer Center Weill Cornell Medical College Overview What is
More informationPIK3CA Mutations in HER2-Positive Breast Cancer
2016.4.29. GBCC PIK3CA Mutations in HER2-Positive Breast Cancer Seock-Ah Im, MD, PhD. Department of Internal Medicine Seoul National University Hospital Contents Introduction TCGA data HER2 signaling pathway
More informationASCO and San Antonio Updates
ASCO and San Antonio Updates 30 th Annual Miami Breast Cancer Conference March 7-10, 2013 Debu Tripathy, MD Professor of Medicine University of Southern California Norris Comprehensive Cancer Center Breakthroughs
More informationBest of San Antonio 2008
Best of San Antonio 2008 Ellie Guardino, MD/PhD Assistant Professor Stanford University BIG 1 98: a randomized double blind phase III study evaluating letrozole and tamoxifen given in sequence as adjuvant
More informationPoint of View on Early Triple Negative
Point of View on Early Triple Negative Valentina Rossi, MD UOSD Oncologia dei Tumori della Mammella Azienda Ospedaliera S.Camillo-Forlanini VRossi@scamilloforlanini.rm.it Outline Neoadjuvant Setting IPSY-2
More informationIdeal neo-adjuvant Chemotherapy in breast ca. Dr Khanyile Department of Medical Oncology, University of Pretoria
Ideal neo-adjuvant Chemotherapy in breast ca Dr Khanyile Department of Medical Oncology, University of Pretoria When is neo-adjuvant Chemo required? Locally advanced breast ca: - Breast conservative surgery
More informationHer 2 Positive Advanced Breast Cancer: From Evidence to Practice
Her 2 Positive Advanced Breast Cancer: From Evidence to Practice Sunil Verma MD, FRCP(C) Medical Director, Tom Baker Cancer Center Professor and Head, Department of Oncology Cumming School of Medicine,
More informationLocally Advanced Breast Cancer: Systemic and Local Therapy
Locally Advanced Breast Cancer: Systemic and Local Therapy Joseph A. Sparano, MD Professor of Medicine & Women s Health Albert Einstein College of Medicine Associate Chairman, Department of Oncology Montefiore
More informationImmunotherapy in breast cancer. Carmen Criscitiello, MD, PhD European Institute of Oncology Milan, Italy
Immunotherapy in breast cancer Carmen Criscitiello, MD, PhD European Institute of Oncology Milan, Italy Outline Rational for immune-based therapy in breast cancer Immunogenic chemotherapy Targeting immune
More informationFDA Briefing Document Oncologic Drugs Advisory Committee Meeting. September 12, sbla /51 Pertuzumab (PERJETA ) Applicant: Genentech, Inc.
/51 FDA Briefing Document Oncologic Drugs Advisory Committee Meeting September 12, 2013 /51 Pertuzumab (PERJETA ) Applicant: Genentech, Inc. Disclaimer: The attached package contains background information
More informationPostoperative Adjuvant Chemotherapies. Stefan Aebi Luzerner Kantonsspital
Postoperative Adjuvant Chemotherapies Stefan Aebi Luzerner Kantonsspital stefan.aebi@onkologie.ch Does Chemotherapy Work in Older Patients? ER : Chemotherapy vs nil Age
More informationOvercoming resistance to endocrine or HER2-directed therapy
Overcoming resistance to endocrine or HER2-directed therapy Jane Lowe Meisel, MD Assistant Professor of Hematology and Medical Oncology Winship Cancer Institute at Emory University 1 Background While most
More informationEarly Stage Disease. Hope S. Rugo, MD Professor of Medicine Director Breast Oncology and Clinical Trials Education UCSF Comprehensive Cancer Center
SABCS 2014: Early Stage Disease Hope S. Rugo, MD Professor of Medicine Director Breast Oncology and Clinical Trials Education UCSF Comprehensive Cancer Center Topics for Discussion Chemotherapy plus 10
More informationEvolving Insights into Adjuvant Chemotherapy. Joyce O Shaughnessy, MD Baylor Sammons Cancer Center Texas Oncology US Oncology
Evolving Insights into Adjuvant Chemotherapy Joyce O Shaughnessy, MD Baylor Sammons Cancer Center Texas Oncology US Oncology 80 70 60 50 40 30 20 10 0 EBCTCG 2005/6 Overview Control Arms with No Systemic
More informationPost-ESMO 2012: Tamara Rordorf Klinik für Onkologie UniversitätsSpital Zürich T.Rordorf, SAMO Luzern 1
Post-ESMO 2012: Breast Cancer Tamara Rordorf Klinik für Onkologie UniversitätsSpital Zürich 1 Neoadjuvant treatment (in Her-2 positive disease) neoadjuvant trials abstracts: breast sparing surgery, biomarkers,
More informationAdjuvant chemotherapy in older breast cancer patients: how to decide?
Adjuvant chemotherapy in older breast cancer patients: how to decide? H. Wildiers University Hospitals Leuven Belgium Wildiers H, Kunkler I, Lancet Oncol 2007 Biganzoli L, Wildiers H, Lancet Oncol. 2012
More informationRole of chemotherapy in BRCA and Triple negative breast cancer. Fernando Moreno Servicio de Oncología Médica Hospital Clinico San Carlos
Role of chemotherapy in BRCA and Triple negative breast cancer Fernando Moreno Servicio de Oncología Médica Hospital Clinico San Carlos Association between TNBC & germline mutations in BRCA 1/2 TNBC is
More informationConsiderations in Adjuvant Chemotherapy. Joyce O Shaughnessy, MD Baylor Sammons Cancer Center Texas Oncology US Oncology
Considerations in Adjuvant Chemotherapy Joyce O Shaughnessy, MD Baylor Sammons Cancer Center Texas Oncology US Oncology 80 70 60 50 40 30 20 10 0 EBCTCG 2005/6 Overview Control Arms with No Systemic Treatment
More informationBreast cancer treatment
Report from the San Antonio Breast Cancer Symposium Breast cancer treatment Determining the best options for select patient groups Sara Soldera, MD, Resident; Nathaniel Bouganim, MD, FRCPC, Medical Oncologist;
More informationThe Neoadjuvant Model as a Translational Tool for Drug and Biomarker Development in Breast Cancer
The Neoadjuvant Model as a Translational Tool for Drug and Biomarker Development in Breast Cancer Laura Spring, MD Breast Medical Oncology Massachusetts General Hospital Primary Mentor: Dr. Aditya Bardia
More informationADAPT. Adjuvant Dynamic marker- Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early breast cancer
ADAPT Adjuvant Dynamic marker- Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early breast cancer Therapieindikation gesteuert durch prognostische Information
More informationPerspectivas de desarrollo de la inmunoterapia en cáncer de mama hereditario. Luis de la Cruz Merino Oncología Médica HUVMacarena (Sevilla)
Perspectivas de desarrollo de la inmunoterapia en cáncer de mama hereditario Luis de la Cruz Merino Oncología Médica HUVMacarena (Sevilla) Outline Immunology and breast cancer Clinical trials with modern
More informationAdjuvant Chemotherapy + Trastuzumab
Diagnosis and Treatment of Patients with Primary and Metastatic Breast Cancer Adjuvant Chemotherapy + Trastuzumab (Optimal Drugs / Dosage / Trastuzumab) Adjuvant Chemotherapy (Optimal Drugs / Optimal Dosage
More informationTerapia sistemica neoadiuvante: in quali tumori? Quali risultati? Dott. Giacomo Pelizzari
Terapia sistemica neoadiuvante: in quali tumori? Quali risultati? Dott. Giacomo Pelizzari Neoadjuvant Treatment A window of opportunity Rational: Historically proposed to enable breast-conserving surgery
More informationESMO Preceptorship Breast Cancer. Giuseppe Curigliano MD, PhD Breast Cancer Program Division of Early Drug Development Istituto Europeo di Oncologia
ESMO Preceptorship Breast Cancer Giuseppe Curigliano MD, PhD Breast Cancer Program Division of Early Drug Development Istituto Europeo di Oncologia Outline Rational for immune-based therapy in BC How to
More informationImmunoconjugates in Both the Adjuvant and Metastatic Setting
Immunoconjugates in Both the Adjuvant and Metastatic Setting Mark Pegram, M.D. Director, Stanford Breast Oncology Program Co-Director, Molecular Therapeutics Program Trastuzumab Treatment of Breast Tumor
More informationNeoadjuvant and Adjuvant Therapy for HER2 Positive Disease
ADJUVANT AND NEOADJUVANT THERAPY FOR HER2-POSITIVE DISEASE Neoadjuvant and Adjuvant Therapy for HER2 Positive Disease Stephen K. Chia, MD, FRCP(C) OVERVIEW Since the initial description of the HER2 proto-oncogene
More informationNSABP Pivotal Breast Cancer Clinical Trials: Historical Perspective, Recent Results and Future Directions
1 1 NSABP Pivotal Breast Cancer Clinical Trials: Historical Perspective, Recent Results and Future Directions Terry Mamounas, M.D., M.P.H., F.A.C.S. Medical Director, Comprehensive Breast Program UF Health
More informationSystemic Therapy for Locally Advanced Breast Cancer
Systemic Therapy for Locally Advanced Breast Cancer Soo-Chin Lee Head & Senior Consultant Department of Haematology-Oncology National University Cancer Institute, Singapore Clinical Care Senior Principal
More informationJosé Baselga, MD, PhD
i n t e r v i e w José Baselga, MD, PhD Dr Baselga is Physician-in-Chief at Memorial Sloan-Kettering Cancer Center in New York, New York. Tracks 1-15 Track 1 Track 2 Track 3 Track 4 Track 5 Track 6 Track
More informationAnthracyclines for Breast Cancer? Are Adjuvant Anthracyclines Dispensible? Needs to be Answered in a Large Prospective Trial
Anthracyclines for Breast Cancer? Are Adjuvant Anthracyclines Dispensible? Needs to be Answered in a Large Prospective Trial Joanne L. Blum, MD, PhD Baylor-Sammons Cancer Dallas, TX Early Breast Cancer
More informationWhat is the Next Goal for HER2 Targeted Therapy?
What is the Next Goal for HER2 Targeted Therapy? Hope S. Rugo, MD Director, Breast Oncology and Clinical Trials Education University of California San Francisco Helen Diller Family Comprehensive Cancer
More informationNon-anthracycline Adjuvant regimens in Early Breast Cancer. Yeesoo Chae, MD, PhD Medical Oncology Kyungpook National University Medical Center
Non-anthracycline Adjuvant regimens in Early Breast Cancer Yeesoo Chae, MD, PhD Medical Oncology Kyungpook National University Medical Center Contents Role of Anthracyclines in adjuvant treatment EBCTCG2012
More information