The Role of Pathologic Complete Response (pcr) as a Surrogate Marker for Outcomes in Breast Cancer: Where Are We Now?
|
|
- Kristina Davidson
- 5 years ago
- Views:
Transcription
1 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 UF Health Cancer Center at Orlando Health Professor of Surgery, University of Central Florida College of Medicine Clinical Professor of Clinical Sciences, Florida State University College of Medicine
2 Clinical Rationale for Neoadjuvant Chemotherapy Neoadjuvant chemotherapy is the standard of care for patients with locally advanced breast cancer A reasonable alternative to adjuvant chemotherapy for those with large operable disease Several randomized clinical trials have shown no significant differences in outcomes between neoadjuvant and adjuvant chemotherapy
3 Pathologic Complete Response (pcr): A Surrogate Endpoint for NC Efficacy Patients who achieve pcr following NC have significantly better outcomes than those who do not As a result pcr has become a surrogate endpoint for NC efficacy Recently, the FDA identified pcr as an endpoint that can be utilized for accelerated approval of new agents for the neoadjuvant treatment of breast cancer
4 Effect of pcr on Overall Survival NSABP B-18 NSABP B-27 Rastogi et al. J Clin Oncol 2008
5 CTNeoBC Meta-Analysis: Association of pcr with EFS and OS HR=0.48, P* < HR=0.36, P* < pcr=ypt0/is ypn0 * Nominal p-value Cortazar P, et al: SABCS 2012
6 CTNeoBC Meta-Analysis: Various Definitions of pcr No evidence of tumor in the breast and negative axillary nodes (ypt0 ypn0) No tumor or in situ tumor only in the breast and negative axillary nodes (ypt0/is ypn0) (Preferred FDA definition) No tumor/in situ tumor only in the breast irrespective of axillary nodal status (ypt0/is) Cortazar P, et al: SABCS 2012
7 Event-free Probability Survival Probability CTNeoBC Meta-Analysis: Which pcr Definition is Best Associated with Long Term Outcome? Event-free Survival Overall Survival ypt0 ypn0 n 1554 ypt0/is ypn0 n 2131 ypt0/is n 2598 pcr vs. no pcr HR= 0.44 pcr vs. no pcr HR= 0.48 pcr vs. no pcr HR= 0.60 ypt0 ypn0 n 1554 ypt0/is ypn0 n 2131 ypt0/is n 2598 pcr vs. no pcr HR= 0.36 pcr vs. no pcr HR= 0.36 pcr vs. no pcr HR= Months since Randomization Months since Randomization
8 Percent with pcr CTNeoBC Meta Analysis: pcr Rates by Tumor Subtype _ HR+/HER2- HR+/HER2+ HR-/HER2+ HR-/HER2- Grade 1,2 Grade 3 No Tras Yes Tras No Tras Yes Tras Cortazar P, et al: SABCS 2012
9 In which Breast Cancer Subtypes Does pcr Associate with Long Term Outcome?
10 CTNeoBC Meta-Analysis: Association of pcr with EFS in HR+/HER2- Subtype
11 CTNeoBC Meta-Analysis: Association of pcr with EFS in HER2+ Subtype
12 CTNeoBC Meta-Analysis: Association of pcr with EFS with/ without Trastuzumab
13 CTNeoBC Meta-Analysis: Association of pcr with EFS in HR-/HER2- Subtype
14 What Magnitude of pcr Improvement in a Randomized Trial Will Predict Long Term Clinical Benefit (EFS and OS Improvement)?
15 Perfect Scenario Example Correlation Between Change in pcr and Improvement in EFS (Simulated Data)
16 CTNeoBC Meta-Analysis: Magnitude of Improvement in pcr Rate Did Not Predict EFS and OS Effect
17 CTNeoBC Meta-Analysis: Possible Reasons for Lack of Correlation Between Improvement in pcr Rates and EFS and OS Effect Low pcr rates Heterogeneity of the population Lack of targeted therapies (except in the NOAH trial) Larger pcr differences between treatment arms are needed to translate into long-term outcome and may vary according to breast cancer subtype
18 NSABP B-27 Schema Operable Breast Cancer (2411 pts) Randomization AC x 4 Tam X 5 Yrs AC x 4 Tam X 5 Yrs AC x 4 Tam X 5 Yrs Surgery Docetaxel x 4 Surgery Surgery Docetaxel x 4
19 NSABP B-27:Pathologic Response in Breast and Axillary Nodes pcr in Breast Positive Nodes No Tumor P < % 13.7% 3.9% AC (1,492 pts) Non-Invasive 25.6% 18.7% 6.9% AC Docetaxel (718 pts) % AC P < AC Docetaxel Bear H, et al: J Clin Oncol, 2003
20 % Disease-free NSABP B-27: Disease-Free Survival TRT N Events AC AC T S HR=0.86 p=0.10 AC S T HR=0.91 p= Years after Surgery Bear H et al: J Clin Oncol 2006
21 pcr Rates and Adjuvant Chemotherapy Efficacy 60% 50% 40% 30% 20% Sign. in DFS,OS Sign. in DFS,OS 25-30% Sign. in DFS,OS 40-45% HER2+??? DFS, OS 50-60% 50-55% HER2+ TNBC 10% 0 7-8% CMFbased 15% Anthrabased Anthra/ Taxanebased Chemo + Traz based Chemo + Dual Anti-HER2 based Anthra/ Taxane- Based + Carbo
22 Neo-ALTTOStudy Design Invasive operable HER2+ BC T > 2 cm (inflammatory BC excluded) LVEF 50% N=450 Stratification: T 5 cm vs. T > 5 cm ER or PgR + vs. ER & PgR N 0-1 vs. N 2 Conservative surgery or not R A N D O M I Z E 6 wks lapatinib paclitaxel trastuzumab paclitaxel lapatinib trastuzumab paclitaxel S U R G E R Y F E C lapatinib trastuzumab lapatinib trastuzumab + 12 wks 34 weeks 52 weeks of anti-her2 therapy X 3
23 NeoALTTO Efficacy - pcr and tpcr L: lapatinib; T: trastuzumab; L+T: lapatinib plus trastuzumab pcr pathologic complete response
24 Design 1: Sequential anti Her2 Rx post chemo N=4602 ALTTO Trial Design 2: Concurrent anti Her2 Rx post anthra N=3337 First interim analysis Aug 11; L v T crossed futility boundaries
25 ALTTO: Changed Analysis Plan (N=6281) P < for DFS statistical significance Piccart, M: ASCO 2014
26 ALTTO: Disease-Free Survival % 86% 70 L+T v T HR.84 P= Median Follow Up: 4.5 yrs Piccart, M: ASCO 2014
27 NSABP B-41: Neoadjuvant Study with Lapatinib vs. Trastuzumab vs. Combo 27 Tissue for Biomarkers Tissue for Biomarkers Operable Breast Cancer HER-2 neu Positive R AC TH AC TL AC THL S U R G E R Y Endpoints: pcr, cardiac events, DFS, OS Trastuzumab for a total of 1 year Accrual: 529 pts
28 NSABP B-41: pcr Breast and Nodes (ypto/isypn0) P=0.056 P=0.78
29 NeoSphere Primary Outcome Measure: pcr* 100% 80% 60% 40% 20% 0% P = P = P = % 29% 17% 24% pcr TH n = 107 THP n = 107 HP n = 107 TP n = 96 *Pathologic complete response (pcr) rate defined as the absence of invasive cancer in the breast at the time of surgery. T = docetaxel; H = trastuzumab, P = pertuzumab. Gianni L et al. Lancet. 2012;13:25-32.
30 Pathologic complete response (%) TRYPHAENA Pathologic Complete Response ypt0/is FEC+H+P x3 T+H+P x3 (n = 73) FEC x3 T+H+P x3 (n = 75) TCH+P x6 (n = 77) FEC, 5-fluorouracil, epirubicin, cyclophosphamide; H, trastuzumab; P, pertuzumab; T, docetaxel; TCH, docetaxel/carboplatin/trastuzumab Schneeweiss A, et al: San Antonio 2011
31 TRYPHAENA: Pathologic Complete Response by HR-Status Pathologic complete response (%) ER- and PR-negative ypt0/is ER- and/or PR-positive FEC+H+P x3 T+H+P x3 (n = 73) FEC x3 T+H+P x3 (n = 75) TCH+P x6 (n = 77) ER, estrogen receptor; FEC, 5-fluorouracil, epirubicin, cyclophosphamide; H, trastuzumab; P, pertuzumab; PR, progesterone receptor; T, docetaxel; TCH, docetaxel/carboplatin/trastuzumab Schneeweiss A, et al: San Antonio 2011
32 % Event-Free B-31/N9831 Joint Analysis Disease-Free Survival ER and/or PR Positive ER and PR Negative AC P AC P AC P+H AC P+H N Events xx% xx% AC P AC P+H AC P+H AC P N Events xx% xx% HR: 0.61 (95%CI: ) HR: 0.62 (95%CI: ) Years from Randomization No. at risk Romond E et al: San Antonio 2012
33 How Do Utilize pcr to Maximize the Clinical Impact Of NC? Use pcr as a surrogate endpoint for long-term outcome (potential pathway for new drug approval) Identify better predictors of pcr: Baseline Early During treatment Use primary tumor response as a guide for tailoring systemic therapy and loco-regional therapy
34 Clinical and Pathologic Response to NC as a Guide for Tailoring Systemic Rx
35 Using Clinical and Path Response to NC as a Guide of Further Systemic Rx Development of multiple active drugs or regimens has lead to the following testable hypotheses: Achievement of pcr with more active regimens will continue to correlate with improved outcome Tumors that do not respond to the original neoadjuvant regimen may respond other active non-cross resistant regimens used either as neoadjuvant or post-neoadjuvant therapy (i.e. resistance is regimen- or drug-specific)
36 Sequential Docetaxel After Anthracycline-Based Neoadjuvant Chemotherapy: Aberdeen Trial First Phase Second Phase Response ITT All Patients 55 pts 4 cycles of Docetaxel cresp. presp. 47% 2% N = cycles of CVAP T 2 (> 3cm), T 3, T 4, T x N 2 R A N D O M I Z E 4 cycles of Docetaxel 52 pts 4 cycles of CVAP 85% 31% p=0.001 p= % 15% 52 pts Smith IC: J Clin Oncol; 2002
37 In Vivo Chemosensitivity-Adapted Neoadjuvant Chemotherapy: the GEPAR-TRIO Trial Sonography N=2072 Core biopsy: uni/bilateral ct2-4a-d cn0-3 size 2 cm* *low risk patients were excluded (T2 + ER/PR pos. + cno + G1/2 + > 35 yrs) Von Minckwitz G et al, SABCS 2011 NC CR/ PR R R NX von Minckwitz et al, JNCI 100: 542, 2008 von Minckwitz et al. JNCI 100; 552, 2008 TACx6 Conventional arms TACx6 TACx8 Responseguided arms
38 Short Term Efficacy (pcr = ypt0 ypn0) 30% Responders N=1344 P=0.27 Non-Responders N=604 P= % 10% TACx6 TACx8 5.3 TACx6 6.0 TAC-NX Von Minckwitz G et al, SABCS 2011 von Minckwitz et al, JNCI 100: 542, 2008 von Minckwitz et al. JNCI 100; 552, 2008
39 DFS and OS after Conventional (TACx6) vs. Response-guided (TACx8/TAC-NX) Treatment Median follow up 62 months Von Minckwitz G et al, J Clin Oncol 2013
40 DFS after TACx6 vs. TACx8 in Responding Patients Von Minckwitz G et al, J Clin Oncol 2013
41 DFS after TACx6 vs. TAC-NX in Non-Responding Patients Von Minckwitz G et al, J Clin Oncol 2013
42 GEPAR-TRIO: pcr Rates by Subtype pcr (%) Luminal A (N=572) Luminal B (HER2-) Luminal B (HER2+) HER2+ (nonluminal) Triple-negative (N=211) (N=281) (N=178) N=362) HR+, HER2-, G1/2 HR+, HER2-, G3 HR+, HER2+ HR-, HER2+ HR-, HER2- Von Minckwitz G et al, J Clin Oncol 2013
43 DFS in Luminal A Tumors by pcr by Treatment Von Minckwitz G et al, J Clin Oncol 2013
44 DFS in Luminal B (HER2-) by pcr by Treatment Von Minckwitz G et al, J Clin Oncol 2013
45 DFS in Luminal B (HER2+) Tumors by pcr by Treatment Von Minckwitz G et al, J Clin Oncol 2013
46 DFS in HER2+(non-luminal) Tumors by pcr by Treatment Von Minckwitz G et al, J Clin Oncol 2013
47 DFS in Triple Negative Tumors by pcr by Treatment Von Minckwitz G et al, J Clin Oncol 2013
48 GeparTrio: Conclusions Interim response-guided (longer or sequential) neoadjuvant chemotherapy improved survival Treatment effects on survival derived from luminal-type tumors This treatment effect could not be predicted by pcr as these tumors have lower pcr rates and their prognosis does not depend on pcr Patients with HER2+ or triple-negative tumors did not benefit from response-guided treatment pcr is highly prognostic in these subgroups Lack of treatment effect on pcr rate corresponds to lack of long term treatment effect Von Minckwitz G et al, J Clin Oncol 2013
49 Post-Neoadjuvant Trial Setting Is Ideal for Evaluating New Agents Enroll only high risk patients with tumors that are proven to be resistant to existing therapies Experimental therapy justified Adjuvant setting with standard clinical endpoints recognized by FDA High event rate Small sample size, short follow up Prognostic profiling data from cells that matters (chemo-resistant cells)
50 NSABP B-50I: KATHERINE Study Schema SURGERY Preoperative therapy: Trastuzumab/ Taxane ± Anthracycline Residual invasive tumor Herceptin T-DM1 Radiation per standard guidance; hormone therapy if ER or PgR pos
51 NSABP B-54-I: Penelope N=800 pts. with HR+/HER2- breast cancer No pcr and CPS-EG score 3 : Palbociclib 125 mg once daily p.o. d1-21, q29 for 12 cycles Neoadjuvant Chemotherapy Surgery +/- Radiotherapy R Placebo d1-21, q29 for 12 cycles Concomitant endocrine therapy according to local standards
52 Clinical and Pathologic Response to NC as a Guide of Further Loco-Regional Rx
53 Individualizing Loco-Regional Therapy with Neoadjuvant Chemotherapy Achievements Conversion of patients with inoperable tumors to operable candidates Conversion of mastectomy candidates to candidates for breast conserving surgery Improvement in cosmesis by reducing the size of lumpectomy in breast conserving surgery candidates with large tumors
54 Individualizing Loco-Regional Therapy with Neoadjuvant Chemotherapy Promises Reduction in the extent of axillary surgery by down-staging involved axillary nodes (SNB) Reduction in the extent of loco-regional XRT by down-staging primary tumors and axillary nodes Potential for eliminating some loco-regional therapy altogether (surgery or XRT) with use of more active regimens and/or appropriate patient selection (imaging/biomarkers)
55 Recently Activated U.S. Clinical Trials 55
56 Questions? 56
57
NeoadjuvantTreatment 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 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 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 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 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 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 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 informationLoco-Regional Management After Neoadjuvant Chemotherapy
1 Loco-Regional Management After Neoadjuvant Chemotherapy Terry Mamounas, M.D., M.P.H., F.A.C.S. Medical Director, Comprehensive Breast Program UF Health Cancer Center at Orlando Health Professor of Surgery,
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 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 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 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 informationImpact of BMI on pathologic complete response (pcr) following neo adjuvant chemotherapy (NAC) for locally advanced breast cancer
Impact of BMI on pathologic complete response (pcr) following neo adjuvant chemotherapy (NAC) for locally advanced breast cancer Rachna Raman, MD, MS Fellow physician University of Iowa hospitals and clinics
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 informationLoco-Regional Management After Neoadjuvant Chemotherapy
1 Loco-Regional Management After Neoadjuvant Chemotherapy Terry Mamounas, M.D., M.P.H., F.A.C.S. Medical Director, Comprehensive Breast Program UF Health Cancer Center at Orlando Health Professor of Surgery,
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 informationNeoadjuvant therapy a new pathway to registration?
Neoadjuvant therapy a new pathway to registration? Graham Ross, FFPM Clinical Science Leader Roche Products Ltd Welwyn Garden City, UK (full time employee) Themes Neoadjuvant therapy Pathological Complete
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 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 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 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 informationRethinking neoadjuvant therapy: neoadjuvant therapy as a platform for drug development in HER2 positive breast cancer
2016.04.29 GBCC luncheon symposium Rethinking neoadjuvant therapy: neoadjuvant therapy as a platform for drug development in HER2 positive breast cancer Seoul National University Bundang Hospital Seoul
More informationSupplementary appendix
Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Cortazar P, Zhang L, Untch M, et al. Pathological
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 informationTaking NeoadjuvantTreatment into the Clinic
Taking NeoadjuvantTreatment into the Clinic The Data and the Challenges Karen A Gelmon MD FRCPC Professor Medicine University of British Columbia Medical Oncologist BC Cancer Agency NeoadjuvantTherapy
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 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 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 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 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 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 informationM D..,., M. M P.. P H., H, F. F A.. A C..S..
Implications of NSABP B-32 and Loco-Regional Therapy Considerations After Neoadjuvant Chemotherapy Terry Mamounas, M.D., M.P.H, F.A.C.S. Professor of Surgery Northeastern Ohio Medical University Medical
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 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 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 informationThe Expert Thoughts. Alessandra Fabi Oncologia Medica 1
The Expert Thoughts Alessandra Fabi Oncologia Medica 1 My Thoughts Neoadjuvant: from the lessons of the history Adjuvant: Escalation and De-escalation Advanced and HER2+ : field for immunomodulation Brain
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 informationLooking Beyond the Standard-of- Care : The Clinical Trial Option
1 Looking Beyond the Standard-of- Care : The Clinical Trial Option Terry Mamounas, M.D., M.P.H., F.A.C.S. Medical Director, Comprehensive Breast Program UF Health Cancer Center at Orlando Health Professor
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 informationDRAFT GUIDANCE. This guidance document is being distributed for comment purposes only.
Guidance for Industry Pathologic Complete Response in Neoadjuvant Treatment of High-Risk Early-Stage Breast Cancer: Use as an Endpoint to Support Accelerated Approval DRAFT GUIDANCE This guidance document
More informationBreast : ASCO Abstracts for Review
Breast : ASCO 2011 Susana Campos, MD, MPH Dana Farber Cancer Institute Abstracts for Review Prevention Neoadjuvant Metastatic Brain mets LBA 504: Exemestane for primary prevention of breast cancer in postmenopausal
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 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 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 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 informationthat the best available evidence has not demonstrated that pcr can predict long-term outcomes in the neoadjuvant setting.
pcr in one arm of a randomized clinical trial comparing two neoadjuvant chemotherapies predicts for improved event-free or overall survival in that arm of the clinical trial. perc noted that the NeoALTTO
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 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 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 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 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 information(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 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 informationEvaluation of Pathologic Response in Breast Cancer Treated with Primary Systemic Therapy
Evaluation of Pathologic Response in Breast Cancer Treated with Primary Systemic Therapy Eun Yoon Cho, MD, PhD Department of Pathology and Translational Genomics Samsung Medical Center Sungkyunkwan University
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 informationGenomic Profiling of Tumors and Loco-Regional Recurrence
1 Genomic Profiling of Tumors and Loco-Regional Recurrence Terry Mamounas, M.D., M.P.H., F.A.C.S. Medical Director, Comprehensive Breast Program UF Health Cancer Center at Orlando Health Professor of Surgery,
More informationUK Interdisciplinary Breast Cancer Symposium. Should lobular phenotype be considered when deciding treatment? Michael J Kerin
UK Interdisciplinary Breast Cancer Symposium Should lobular phenotype be considered when deciding treatment? Michael J Kerin Professor of Surgery National University of Ireland, Galway and Galway University
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 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 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 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 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 informationSan Antonio Breast Cancer Symposium, December 5-9, San Antonio Breast Cancer Symposium, December 5-9, 2017
San Antonio Breast Cancer Symposium, December 5-9, 2017 Survival analysis of the prospectively randomized phase III GeparSepto trial comparing neoadjuvant chemotherapy with weekly nab-paclitaxel with solvent-based
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 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 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 (Primary) Systemic Therapy
Diagnosis and Treatment of Patients with Primary and Metastatic reast Cancer Neoadjuvant (Primary) Systemic Therapy Neoadjuvant Systemic Therapy Versions 2002 2017: auerfeind / lohmer / Costa / Dall /
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 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 informationNeoadjuvant Treatment of. of Radiotherapy
Neoadjuvant Treatment of Breast Cancer: Role of Radiotherapy Neoadjuvant Chemotherapy Many new questions for radiation oncology? lack of path stage to guide indications should treatment response affect
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 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 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 informationNeoadjuvant systemic therapy: Practice, patient and research considerations
Neoadjuvant systemic therapy: Practice, patient and research considerations Dr Nicholas Zdenkowski BMed, FRACP, ClinDipPallCare, GradDipClinEpi Medical Oncologist/Clinical Research Fellow Calvary Mater
More informationOPTIMIZING NONANTHRACYLINES FOR EARLY BREAST CANCER. Stephen E. Jones, M.D. US Oncology Research, McKesson Specialty Health The Woodlands, Tx
OPTIMIZING NONANTHRACYLINES FOR EARLY BREAST CANCER Stephen E. Jones, M.D. US Oncology Research, McKesson Specialty Health The Woodlands, Tx ANTHRACYCLINES AND TAXANES ARE COMMONLY USED USED IN MOST REGIMENS
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 informationClinical Management Guideline for Breast Cancer
Initial Evaluation Clinical Stage Pre-Treatment Evaluation Treatment and pathological stage Adjuvant Treatment Less than 4 positive lymph nodes ER Positive HER2 Negative (see page 2 & 3 ) Primary Diagnosis:
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 informationControversies in Breast Pathology ELENA PROVENZANO ADDENBROOKES HOSPITAL, CAMBRIDGE
Controversies in Breast Pathology ELENA PROVENZANO ADDENBROOKES HOSPITAL, CAMBRIDGE Neoadjuvant Chemotherapy Indications: Management of locally advanced invasive breast cancers including inflammatory breast
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 informationPage 1. AHN-JHU Breast Cancer Symposium. Novel Local Regional Clinical Trials. Background. Neoadjuvant Chemotherapy Benefit.
AHN-JHU Breast Cancer Symposium Novel Local Regional Clinical Trials March 22, 2019 Thomas B. Julian, MD, FACS Associate Medical Director, Cancer Program Development, ANH Cancer Institute Background In
More informationNeoadjuvant chemotherapy: what does it take to tango?
Breast Cancer Neoadjuvant chemotherapy: what does it take to tango? Nicholas Zdenkowski 1,2, Nicole McCarthy 3,4 1 Australia and New Zealand Breast Cancer Trials Group, NSW, Australia; 2 University of
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 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 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 information非臨床試験 臨床の立場から 京都大学医学部附属病院戸井雅和
資料 2 2 非臨床試験 臨床の立場から 京都大学医学部附属病院戸井雅和 1 Preclinical studies Therapeutic Window: Efficacy/Toxicity Disease Specificity Subtype Specificity Combination: Concurrent/Sequential Therapeutic situation: Response/
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 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 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 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 informationAdjuvant Systemic Therapy in Early Stage Breast Cancer
Adjuvant Systemic Therapy in Early Stage Breast Cancer Julie R. Gralow, M.D. Director, Breast Medical Oncology Jill Bennett Endowed Professor of Breast Cancer Professor, Global Health University of Washington
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 informationDR LUIS MANSO UNIDAD TUMORES DE MAMA Y GINECOLÓGICOS HOSPITAL 12 DE OCTUBRE MADRID
DR LUIS MANSO UNIDAD TUMORES DE MAMA Y GINECOLÓGICOS HOSPITAL 12 DE OCTUBRE MADRID RESUMEN DE ARTICULOS THERESA BOLERO 3 NOAH UP-DATE GEPAR SIXTO RADIOTHERAPY EBCTCG CTCs MISCELANEAS Lancet Oncol 2014;
More informationBreast Cancer Breast Managed Clinical Network
Initial Evaluation Clinical Stage Pre-Treatment Evaluation Treatment and pathological stage Less than 4 positive lymph nodes Adjuvant Treatment ER Positive HER2 Negative (see page 2 & 3 ) HER2 Positive
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 information4, :00 PM 9:00 PM
Consensus or Controversy? Clinical Investigators Provide Their Perspectives on Practical Issues and Research Questions in the Management of Breast Cancer Robert W Carlson, MD John Crown, MD Charles E Geyer
More informationORMONOTERAPIA ADIUVANTE: QUALE LA DURATA OTTIMALE? MARIANTONIETTA COLOZZA
ORMONOTERAPIA ADIUVANTE: QUALE LA DURATA OTTIMALE? MARIANTONIETTA COLOZZA THE NATURAL HISTORY OF HORMONE RECEPTOR- POSITIVE BREAST CANCER IS VERY LONG Recurrence hazard rate 0.3 0.2 0.1 0 ER+ (n=2,257)
More informationThe absolute benefit from chemotherapy for both older and younger patients appeared most significant in ER-negative populations.
Hello, my name is Diane Hecht, and I am a Clinical Pharmacy Specialist at the University of Texas MD Anderson Cancer Center. It s my pleasure to talk to you today about the role of chemotherapy in this
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 information