Technology Hurdles: Drug Developer Perspective

Size: px
Start display at page:

Download "Technology Hurdles: Drug Developer Perspective"

Transcription

1 Technology Hurdles: Drug Developer Perspective Robert Mass, MD Senior Director Genentech, Inc. June 8, 2009

2 Diagnostic challenges Genentech has been committed to personalized drug development in oncology since Herceptin In spite of this commitment, our efforts to improve the lives of individual patients have been challenged by: The differential pace of therapeutic drug development/innovation when compared to diagnostic innovation Example: Herceptin and HER2 testing The technical challenges of pre-clinical to clinical diagnostic transition Example: Pertuzumab and HER2 pathway activation The regulatory environment governing the linkage of diagnostic testing and targeted therapy More about that tomorrow Page 2

3 The Herceptin program had a viable biomarker from day Amplification Level : > Disease-free survival probability Not amplified (n = 52) Amplified (n = 11) > 5 copies 12.5 kb kb - p185 - Southern Northern Western Time (months) Frozen IHC 27% 63% % Women 10% Slamon et al., Science 235: , 1987 Slamon et al., Science 244: , 1989

4 The Herceptin program had a viable biomarker from day 1 HER2 Expression Level SK-BR-3 BT-474 MDA-MB-361 MDA-MB-453 MDA-MB-436 ZR-75-1 MDA-MB-231 MCF Cell line HER2/cell* IHC score FISH Score MDA , MDA , MDA-361 ~ ~4 SK-BR BR-3 2,390, ~8 * Scatchard analysis Growth Inhibition (%) Antibody Inhibiton (4D5) of Anchorage-Independent Growth Is Related to HER2 Expression Level HER2 IHC score is directly correlated to HER2 density and amplification

5 And The Rest is History Probability of Survival Risk ratio = % Cl = 0.64, 1.00 Herceptin + Chemo (n = 235) Chemo Alone (n = 234) Months

6 But not so Fast...FISH is here! Orange: Green: HER-2/ 2/neu Chromosome 17 centromere < 2.0 Not Amplified (FISH-) 2.0 Amplified (FISH+)

7 FISH score distribution in the pivotal Herceptin study 27.9% of study patients were not HER2 amplified Number of Cases FISH Ratios 20

8 Outcome by FISH score in the pivotal Herceptin study FISH+ FISH - Probability of Survival Herceptin + Chemo (n = 164) Risk ratio = % Cl = 0.53, 0.91 Chemo Alone (n = 161) Herceptin + Chemo (n = 62) Risk ratio = % Cl = 0.70, 1.63 Chemo Alone (n = 64) Months Months Mass R. et al., Clinical Breast Cancer 6:240-46, 2005

9 What did this entail? Minimizing loss of informative samples Sufficiently validating novel technology Enabled 96% of patients to be included in outcomes analysis Bridging concordance with our FDA approved diagnostic HercepTest vs PathVysion Replicating results 799 samples were analyzed in 2 independent laboratories Time Project initiated in April 1999, FDA approval April 2002 Page 9

10 Where we are now (but what about CISH, qrt-pcr, or the next real [or perceived] innovation?) Page 10

11 Pertuzumab What do you do when you don t have a viable biomarker from the start?

12 Trastuzumab vs Pertuzumab Both anti-her2 antibodies, but distinct epitopes & MOA s Trastuzumab Herceptin Pertuzumab

13 The start of a pertuzumab biomarker 293/HERX LXFE 211 LXFA 289 LXFA 297 LXFE 397 LXFA 526 LXFL 529 LXFA 629 LXFA 1041 LXFL 1072 LXFE 211 LXFA 289 LXFA 297 LXFE 397 LXFA 526 LXFL 529 LXFA 629 LXFA 1041 LXFL 1072 HER1 A HER1/2 HER2 B HER 2/3 HER3 rhumab 2C4 responsive rhumab 2C4 responsive Not associated with HER receptors Associated with HER heterodimers Data: B. Bossenmaier & H. Koll

14 How do we detect HER2 heterodimers in clinical samples? (harder than you think) HER2 activation pher2 Directly detect HER dimers Immunoprecipitation and blotting Heterodimer ELISA Development of heterodimer-specific antibody reagents FRET (fluorescence resonance energy transfer) Proximity assays Surrogate markers for receptor activation Gene expression profile Proteomic profile Downstream regulated gene activity

15 The nearly impossible clinical experiment 1.0 Proportion progression-free Median TTP pher2 positive n= weeks pher2 negative n= weeks pher2 unknown n= weeks All subjects n= weeks All patients treated with pertuzumab Time to disease progression (days) Every patient underwent laparoscopic biopsy for study entry Gordon et al. J Clin Oncol. 2005;23:16S (abstract 5051). Gordon et al. J Clin Oncol. In press.

16 Our next trip to the plate Ovarian cancer Platinum-resistant Gemcitabine + Placebo Gemcitabine + Pertuzumab N= o EP = PFS Control Pertuzumab

17 The ensuing diagnostic interrogation..

18 This is an example of detecting HER2 dimerization via downstream regulated gene activity CTRL HRG Pert + HRG Pert 2.5 6h stimulation Fold CTRL out of 8 OvCa cell lines down-regulate HER3 mrna expression after HRG stimulation

19 Our current trip to the plate in ovarian cancer 1 o EP = PFS Looking for a big treatment effect in a small, selected population

20 But what about HER2 amplification? HER2+ MBC Progressed on Herceptin Herceptin + Pertuzumab 2 R or 1 R + 12 SD or 13 SD in 1 st 24 patients? YES NO Stage 2 (n=66) Stop trial Complete response a 5 (7.6) Partial response a 11 (16.7) Stable disease for 8 cycles (~6 months) n (%) 17 (25.8) Objective response rate 16 (24.2) Clinical benefit rate b 33 (50.0) Gelmon et al. J Clin Oncol 2008;26(15S): Abstract 1026

21 But what about HER2 amplification? CLEOPATRA HER2+ MBC (n=800) Docetaxel + trastuzumab + placebo Docetaxel + trastuzumab + pertuzumab An international Phase III randomized, double-blind, placebo-controlled study (approximately 250 sites worldwide) Enrollment stratified by: Prior treatment for breast cancer Geographic region of enrollment Endpoints: PFS and OS Quality of life Biomarker analysis

22 Conclusions In retrospect, Herceptin was the exception, not the rule This is a lot harder than we thought! A major technologic hurdle remains the availability of appropriately processed tissue for exploratory biomarker assessments FFPE material is a bad platform.most of the time Page 22

23 Our Touchstone: The Diagnostic Iceberg Page 23

Her 2 Positive Metastatic Breast Cancer

Her 2 Positive Metastatic Breast Cancer Her 2 Positive Metastatic Breast Cancer Alison Jones November 2013 Mrs Hermione Positive (then and now!) Diagnosed 2007 T2 N1 Mo ER ve; Her2 ve Mastectomy ANC; FEC/T Herceptin (12months) August 2010metastatic

More information

Policy No: dru281. Medication Policy Manual. Date of Origin: September 24, Topic: Perjeta, pertuzumab. Next Review Date: May 2015

Policy No: dru281. Medication Policy Manual. Date of Origin: September 24, Topic: Perjeta, pertuzumab. Next Review Date: May 2015 Medication Policy Manual Topic: Perjeta, pertuzumab Committee Approval Date: May 9, 2014 Policy No: dru281 Date of Origin: September 24, 2012 Next Review Date: May 2015 Effective Date: June 1, 2014 IMPORTANT

More information

XII Michelangelo Foundation Seminar

XII 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 information

Immunoconjugates in Both the Adjuvant and Metastatic Setting

Immunoconjugates 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 information

HER2-Targeted Rx. An Historical Perspective

HER2-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 information

HER2 status assessment in breast cancer. Marc van de Vijver Academic Medical Centre (AMC), Amsterdam

HER2 status assessment in breast cancer. Marc van de Vijver Academic Medical Centre (AMC), Amsterdam HER2 status assessment in breast cancer Marc van de Vijver Academic Medical Centre (AMC), Amsterdam 13e Bossche Mamma Congres 17 th June 2015 Modern cancer therapies are based on sophisticated molecular

More information

Novel Biomarkers (Kallikreins) for Prognosis and Therapy Response in Ovarian cancer

Novel Biomarkers (Kallikreins) for Prognosis and Therapy Response in Ovarian cancer Novel Biomarkers (Kallikreins) for Prognosis and Therapy Response in Ovarian cancer Eleftherios P. Diamandis, M.D., Ph.D., FRCP(C) EORTC-NCI-ASCO Meeting,November 16, 2007 Yousef GM, Diamandis EP. Endocr.

More information

CANCER. Clinical Validation of Breast Cancer Predictive Markers

CANCER. Clinical Validation of Breast Cancer Predictive Markers Clinical Validation of Breast Cancer Predictive Markers David Hicks, MD Loralee McMahon, MS, HTL(ASCP) CANCER The human body is composed of billions of highly regulated cells Cancer cells no longer respond

More information

XII Michelangelo Foundation Seminar

XII 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 information

The 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 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 information

Janet E. Dancey NCIC CTG NEW INVESTIGATOR CLINICAL TRIALS COURSE. August 9-12, 2011 Donald Gordon Centre, Queen s University, Kingston, Ontario

Janet E. Dancey NCIC CTG NEW INVESTIGATOR CLINICAL TRIALS COURSE. August 9-12, 2011 Donald Gordon Centre, Queen s University, Kingston, Ontario Janet E. Dancey NCIC CTG NEW INVESTIGATOR CLINICAL TRIALS COURSE August 9-12, 2011 Donald Gordon Centre, Queen s University, Kingston, Ontario Session: Correlative Studies in Phase III Trials Title: Design

More information

Corporate Medical Policy

Corporate Medical Policy Corporate Medical Policy Pertuzumab for Treatment of Malignancies File Name: Origination: Last CAP Review: Next CAP Review: Last Review: pertuzumab_for_treatment_of_malignancies 2/2013 4/2017 4/2018 6/2017

More information

Targe:ng HER2 in Metasta:c Breast Cancer in 2014

Targe:ng HER2 in Metasta:c Breast Cancer in 2014 Targe:ng HER2 in Metasta:c Breast Cancer in 2014 Kimberly L. Blackwell MD Professor Department of Medicine and Radia:on Oncology Duke University Medical Center Director, Breast Cancer Program Duke Cancer

More information

A vision for HER2 future

A 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 information

Biomarkers for HER2-directed Therapies : Past Failures and Future Perspectives

Biomarkers 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 information

Update 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 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 information

New Targeted Agents Demonstrate Greater Efficacy and Tolerability in the Treatment of HER2-positive Breast Cancer

New Targeted Agents Demonstrate Greater Efficacy and Tolerability in the Treatment of HER2-positive Breast Cancer New Evidence reports on presentations given at ASCO 2012 New Targeted Agents Demonstrate Greater Efficacy and Tolerability in the Treatment of HER2-positive Breast Cancer Presentations at ASCO 2012 Breast

More information

Welcome! HER2 TESTING DIAGNOSTIC ACCURACY 4/11/2016

Welcome! HER2 TESTING DIAGNOSTIC ACCURACY 4/11/2016 HER2 TESTING DIAGNOSTIC ACCURACY Can t We Finally Get It Right? Allen M. Gown, M.D. Medical Director and Chief Pathologist PhenoPath Laboratories Seattle, Washington Clinical Professor of Pathology University

More information

New Drug Development in HER2+ Breast Cancer

New Drug Development in HER2+ Breast Cancer New Drug Development in HER2+ Breast Cancer Philippe Aftimos, M.D. Senior Research Physician Clinical Pharmacology Unit Institut Jules Bordet Background Amplification of HER2 occurs in approximately 20%

More information

Systemic 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 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 information

Lung Cancer Non-small Cell Local, Regional, Small Cell, Other Thoracic Cancers: The Question Isn t Can We, but Should We

Lung Cancer Non-small Cell Local, Regional, Small Cell, Other Thoracic Cancers: The Question Isn t Can We, but Should We Lung Cancer Non-small Cell Local, Regional, Small Cell, Other Thoracic Cancers: The Question Isn t Can We, but Should We Edward Garon, MD, MS Associate Professor Director- Thoracic Oncology Program David

More information

INDIVIDUALIZED THERAPY OF METASTATIC BREAST CANCER Lance A. Liotta MD PhD

INDIVIDUALIZED THERAPY OF METASTATIC BREAST CANCER Lance A. Liotta MD PhD INDIVIDUALIZED THERAPY OF METASTATIC BREAST CANCER Lance A. Liotta MD PhD A vision for Combining proteomic mapping with genomic analysis of the metastatic lesion 57 year old women TNBC locally recurrent

More information

Herceptin Pivotal Studies

Herceptin Pivotal Studies Herceptin Pivotal Studies Nuhad K Ibrahim, MD, FACP Associate Professor of Medicine Breast Medical Oncology Department MD Anderson Cancer Center Houston, TX, USAE-mail: nibrahim@mdanderson.org Herceptin

More information

HER2/neu Evaluation of Breast Cancer in 2019

HER2/neu Evaluation of Breast Cancer in 2019 HER2/neu Evaluation of Breast Cancer in 2019 A.A. Sahin, M.D. Professor of Pathology and Translation Molecular Pathology Section Chief of Breast Pathology ERBB2 (HER2) Background 185-kDa membrane protein

More information

A Fully Integrated Cancer Company.

A Fully Integrated Cancer Company. A Fully Integrated Cancer Company. Jefferies 2015 Healthcare Conference June 2, 2015 Robert Mulroy, President & CEO Forward Looking Statements To the extent that statements contained in this presentation

More information

FDA Briefing Document Oncologic Drugs Advisory Committee Meeting. September 12, sbla /51 Pertuzumab (PERJETA ) Applicant: Genentech, Inc.

FDA 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 information

Media Release. FDA grants Roche s Perjeta accelerated approval for use before surgery in people with HER2-positive early stage breast cancer

Media Release. FDA grants Roche s Perjeta accelerated approval for use before surgery in people with HER2-positive early stage breast cancer Media Release Basel, 1 October 2013 FDA grants Roche s Perjeta accelerated approval for use before surgery in people with HER2-positive early stage breast cancer The Perjeta regimen is the first treatment

More information

Systemic Therapy of HER2-positive Breast Cancer

Systemic 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

PIK3CA Mutations in HER2-Positive Breast Cancer

PIK3CA 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 information

Advanced HER2+ Breast Cancer: New Options and How to Deploy Them. José Baselga MD, PhD

Advanced HER2+ Breast Cancer: New Options and How to Deploy Them. José Baselga MD, PhD Advanced HER2 Breast Cancer: New Options and How to Deploy Them José Baselga MD, PhD HER2 signaling results in a multitude of cellular effects, including increased cellular proliferation HER2 HER3 RAS

More information

Her 2 Positive Advanced Breast Cancer: From Evidence to Practice

Her 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 information

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

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 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

HER2-positive Breast Cancer

HER2-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 information

Non-hormonal therapies in advanced breast cancer: new and emerging approaches

Non-hormonal therapies in advanced breast cancer: new and emerging approaches Non-hormonal therapies in advanced breast cancer: new and emerging approaches Outline Review goals of treatment Demystify chemotherapy decision making Look at the evidence for improvements over time Discuss

More information

Assessment Run B HER-2

Assessment Run B HER-2 Assessment Run B1 2006 HER-2 The slide to be stained for HER-2 comprised: 1. Cell line JIMT-1 (Amplified)* 2. Cell line MDA-453 (Amplified) 3. Cell line MCF-7 (Not amplified) 4. Cell line BT474 (Amplified)

More information

confirmatory clinical trials - The PMDA Perspective -

confirmatory clinical trials - The PMDA Perspective - EMA workshop on the investigation of subgroups in confirmatory clinical trials The investigation of subgroups in confirmatory clinical trials - The PMDA Perspective - Yuki Ando Senior Scientist for Biostatistics

More information

R&D DAY. June 14, 2016

R&D DAY. June 14, 2016 R&D DAY June 14, 2016 Forward Looking Statement This written and oral presentation contains forward-looking statements, including statements concerning preclinical results and anticipated research, preclinical

More information

Roche s Perjeta regimen approved in Europe for use before surgery in early stage aggressive breast cancer

Roche s Perjeta regimen approved in Europe for use before surgery in early stage aggressive breast cancer Media Release Basel, 31 July, 2015 Roche s Perjeta regimen approved in Europe for use before surgery in early stage aggressive breast cancer The approval is based on the benefit seen with the Perjeta regimen

More information

ACRIN Gynecologic Committee

ACRIN Gynecologic Committee ACRIN Gynecologic Committee Fall Meeting 2010 ACRIN Abdominal Committee Biomarkers & Endpoints in Ovarian Cancer Trials Robert L. Coleman, MD Professor and Vice Chair, Clinical Research Department of Gynecologic

More information

Locoregional treatment Session Oral Abstract Presentation Saulo Brito Silva

Locoregional treatment Session Oral Abstract Presentation Saulo Brito Silva Locoregional treatment Session Oral Abstract Presentation Saulo Brito Silva Background Post-operative radiotherapy (PORT) improves disease free and overall suvivallin selected patients with breast cancer

More information

Accelerated approval of Perjeta for neoadjuvant use also converted to full approval

Accelerated approval of Perjeta for neoadjuvant use also converted to full approval Media Release Basel, 21 December 2017 FDA approves Roche s Perjeta (pertuzumab) for adjuvant treatment of specific type of early breast cancer Accelerated approval of Perjeta for neoadjuvant use also converted

More information

Understanding your biomarker: what this marker can do for you

Understanding your biomarker: what this marker can do for you Understanding your biomarker: what this marker can do for you Dr. John Bartlett/Dr. Harriet Feilotter As is your Pathology, so is your Medicine. Sir William Osler. 1849-1919. Disclosure statement John

More information

Quantitative Assay for Measurement of HER2 Total Protein Expression and HER2 Dimers

Quantitative Assay for Measurement of HER2 Total Protein Expression and HER2 Dimers Quantitative Assay for Measurement of HER2 Total Protein Expression and HER2 Dimers Policy Number: 2.04.76 Last Review: 12/2017 Origination: 12/2015 Next Review: 12/2018 Policy Blue Cross and Blue Shield

More information

MEDICAL POLICY. Proprietary Information of YourCare Health Plan

MEDICAL POLICY. Proprietary Information of YourCare Health Plan MEDICAL POLICY SUBJECT: HER-2 TESTING IN INVASIVE BREAST OR PAGE: 1 OF: 7 If the member's subscriber contract excludes coverage for a specific service it is not covered under that contract. In such cases,

More information

Precision Medicine Lessons from meta-analyses of 70,253 patients

Precision Medicine Lessons from meta-analyses of 70,253 patients Precision Medicine Lessons from meta-analyses of 70,253 patients Razelle Kurzrock, MD Senior Deputy Director, Clinical Science Director, Center for Personalized Cancer Therapy and Clinical Trials Office

More information

Priti Lal, MD, 1 Paulo A. Salazar, 1 Clifford A. Hudis, MD, 2 Marc Ladanyi, MD, 1 and Beiyun Chen, MD, PhD 1. Abstract

Priti Lal, MD, 1 Paulo A. Salazar, 1 Clifford A. Hudis, MD, 2 Marc Ladanyi, MD, 1 and Beiyun Chen, MD, PhD 1. Abstract Anatomic Pathology / DUAL- VS SINGLE-COLOR SCORING IN IMMUNOHISTOCHEMICAL AND FISH HER-2 TESTING HER-2 Testing in Breast Cancer Using Immunohistochemical Analysis and Fluorescence In Situ Hybridization

More information

Design considerations for Phase II trials incorporating biomarkers

Design considerations for Phase II trials incorporating biomarkers Design considerations for Phase II trials incorporating biomarkers Sumithra J. Mandrekar Professor of Biostatistics, Mayo Clinic Pre-Meeting Workshop Enhancing the Design and Conduct of Phase II Studies

More information

Present and emerging treatment options in Her-2/neu overexpressing metastatic breast cancer

Present and emerging treatment options in Her-2/neu overexpressing metastatic breast cancer Present and emerging treatment options in Her-2/neu overexpressing metastatic breast cancer Christoph C. Zielinski Clinical Division of Oncology, Department of Medicine I and Comprehensive Cancer Center,

More information

patients in the era of

patients in the era of Communicating with cancer patients in the era of personalized medicine September 9 th, 2017 Gerald Prager, M.D. Comprehensive Cancer Center Vienna Medical University of Vienna, Austria Gerald Prager, M.D.

More information

Possible causes of difference among regions How to look at the results from MRCT Non-compliance with GCP and/or protocol Apparent Differences (Play of

Possible causes of difference among regions How to look at the results from MRCT Non-compliance with GCP and/or protocol Apparent Differences (Play of Outline ICH E17 General Principles for Planning and Design of Multi-Regional Clinical Trials Future MRCTs Based on E17 Guideline Background and Key Principles in E17 Some case studies of Gastric Cancer

More information

Third Quarter 2015 Earnings Call. November 9, 2015

Third Quarter 2015 Earnings Call. November 9, 2015 Third Quarter 2015 Earnings Call November 9, 2015 Forward-Looking Statements All of the statements in this presentation that are not statements of historical facts constitute forward-looking statements

More information

Reviewer's report. Version: 1 Date: 24 May Reviewer: Cathy Moelans. Reviewer's report:

Reviewer's report. Version: 1 Date: 24 May Reviewer: Cathy Moelans. Reviewer's report: Reviewer's report Title: Validation of HER2 testing with core needle biopsy specimens from primary breast cancers in terms of interobserver reproducibility and concordance with surgically resected specimens

More information

EGFR inhibitors in NSCLC

EGFR inhibitors in NSCLC Suresh S. Ramalingam, MD Associate Professor Director of Medical Oncology Emory University i Winship Cancer Institute EGFR inhibitors in NSCLC Role in 2nd/3 rd line setting Role in first-line and maintenance

More information

When is Chemotherapy indicated in Advanced Luminal Breast Cancer?

When is Chemotherapy indicated in Advanced Luminal Breast Cancer? When is Chemotherapy indicated in Advanced Luminal Breast Cancer? Soo-Chin Lee Head & Senior Consultant Department of Haematology-Oncology Clinical Care National University Cancer Institute, Singapore

More information

José Baselga, MD, PhD

José 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 information

AVANCES EN METODOLOGÍA DE LA INVESTIGACIÓN. Alberto Ocaña Hospital Universitario de Albacete

AVANCES EN METODOLOGÍA DE LA INVESTIGACIÓN. Alberto Ocaña Hospital Universitario de Albacete AVANCES EN METODOLOGÍA DE LA INVESTIGACIÓN Alberto Ocaña Hospital Universitario de Albacete Endpoints PFS as an endpoint Surrogate endpoints PCR-FDA accelerated approval Factors afecting PFS: censoring

More information

PRO: 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 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 information

Controversies in HER2 Oncogene Testing: What Constitutes a True Positive Result in Patients With Breast Cancer?

Controversies in HER2 Oncogene Testing: What Constitutes a True Positive Result in Patients With Breast Cancer? Controversies in HER2 Oncogene Testing: What Constitutes a True Positive Result in Patients With Breast Cancer? Michael F. Press, MD, PhD; Yanling Ma, MD; Susan Groshen, PhD; Guido Sauter, MD, PhD; and

More information

Overcoming resistance to endocrine or HER2-directed therapy

Overcoming 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 information

Cancer du sein métastatique et amélioration de la survie Pr. X. Pivot

Cancer du sein métastatique et amélioration de la survie Pr. X. Pivot Cancer du sein métastatique et amélioration de la survie Pr. X. Pivot Date of preparation: November 2015. EU0250i TTP/PFS Comparaisons First line metastatic breast cancer Monotherapy Docetaxel Chan 1999

More information

Accelerating Innovation in Statistical Design

Accelerating Innovation in Statistical Design Implementing a National Cancer Clinical Trials System for the 21 st Century, Workshop #2 Session #5: Accelerating Innovation Through Effective Partnerships Accelerating Innovation in Statistical Design

More information

Nuovo paradigma terapeutico nel trattamento del carcinoma mammario HER2+ metastatico: dagli studi alla pratica clinica Prima linea di trattamento

Nuovo paradigma terapeutico nel trattamento del carcinoma mammario HER2+ metastatico: dagli studi alla pratica clinica Prima linea di trattamento Nuovo paradigma terapeutico nel trattamento del carcinoma mammario HER2+ metastatico: dagli studi alla pratica clinica Prima linea di trattamento Prof. Sabino De Placido Dip. di Endocrinologia ed Oncologia

More information

Quantitative Assay for Measurement of HER2 Total Protein Expression and HER2 Dimers

Quantitative Assay for Measurement of HER2 Total Protein Expression and HER2 Dimers Quantitative Assay for Measurement of HER2 Total Protein Expression and HER2 Dimers Policy Number: 2.04.76 Last Review: 12/2018 Origination: 12/2015 Next Review: 12/2019 Policy Blue Cross and Blue Shield

More information

Targeted Agents as Maintenance Therapy. Karen Kelly, MD Professor of Medicine UC Davis Cancer Center

Targeted Agents as Maintenance Therapy. Karen Kelly, MD Professor of Medicine UC Davis Cancer Center Targeted Agents as Maintenance Therapy Karen Kelly, MD Professor of Medicine UC Davis Cancer Center Disclosures Genentech Advisory Board Maintenance Therapy Defined Treatment Non-Progressing Patients Drug

More information

The issues that will be resolved through PMCs include the the requalification of bioburden test.

The issues that will be resolved through PMCs include the the requalification of bioburden test. BLA 125409/0_ Perjeta (pertuzumab) 4 patients with normal renal function. No dose adjustment can be recommended for patients with severe renal impairment because of the limited pharmacokinetic data available.

More information

Treatment of Metastatic Breast Cancer. Prof RCCoombes Imperial College London

Treatment of Metastatic Breast Cancer. Prof RCCoombes Imperial College London Treatment of Metastatic Breast Cancer Prof RCCoombes Imperial College London Metastatic Breast Cancer: General Guidelines Specialized oncology nurses (if possible specialized breast nurses) should be part

More information

Circulating tumor cells as biomarker for hormonal treatment in breast and prostate cancer. Michal Mego

Circulating tumor cells as biomarker for hormonal treatment in breast and prostate cancer. Michal Mego National Cancer Institute, Slovakia Translational Research Unit Circulating tumor cells as biomarker for hormonal treatment in breast and prostate cancer Michal Mego 2 nd Department of Oncology, Faculty

More information

Outline of the presentation

Outline of the presentation Outline of the presentation Breast cancer subtypes and classification Clinical need in estrogen-positive (ER+) metastatic breast cancer (mbc) Sulforaphane and SFX-01: the preclinical evidence STEM Phase

More information

Maintenance Therapy for Advanced NSCLC: When, What, Why & What s Left After Post-Maintenance Relapse?

Maintenance Therapy for Advanced NSCLC: When, What, Why & What s Left After Post-Maintenance Relapse? Maintenance Therapy for Advanced NSCLC: When, What, Why & What s Left After Post-Maintenance Relapse? Mark A. Socinski, MD Professor of Medicine Multidisciplinary Thoracic Oncology Program Lineberger Comprehensive

More information

Development of Rational Drug Combinations for Oncology Indications - An Industry Perspective

Development of Rational Drug Combinations for Oncology Indications - An Industry Perspective Development of Rational Drug Combinations for Oncology Indications An Industry Perspective Stuart Lutzker, MDPhD Vice President Oncology Early Development Genentech Inc 1 Conventional Oncology Drug Development

More information

Media Release. Basel, 3 June 2012

Media Release. Basel, 3 June 2012 Media Release Basel, 3 June 2012 Roche s targeted investigational breast cancer medicine, trastuzumab emtansine (T-DM1), reduced the risk of cancer worsening or death by 35 percent in pivotal phase III

More information

Dr. dr. Primariadewi R, SpPA(K)

Dr. dr. Primariadewi R, SpPA(K) Curriculum Vitae Dr. dr. Primariadewi R, SpPA(K) Education : Medical Doctor from UKRIDA Doctoral Degree from Faculty of Medicine University of Indonesia Pathologist Specialist and Consultant from Faculty

More information

Media Release. FDA grants Priority Review for Roche s Perjeta (pertuzumab) for adjuvant treatment of HER2-positive early breast cancer

Media Release. FDA grants Priority Review for Roche s Perjeta (pertuzumab) for adjuvant treatment of HER2-positive early breast cancer Media Release Basel, 29 September 2017 FDA grants Priority Review for Roche s Perjeta (pertuzumab) for adjuvant treatment of HER2-positive early breast cancer Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced

More information

DR. BOMAN N. DHABHAR Consulting Oncologist Jaslok Hospital, Fortis Hospital Mulund, Wockhardt Hospital Mumbai & BND Onco Centre INDIA

DR. 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 information

The Role of Pathologic Complete Response (pcr) as a Surrogate Marker for Outcomes in Breast Cancer: Where Are We Now?

The 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 information

Objectives. Briefly summarize the current state of colorectal cancer

Objectives. Briefly summarize the current state of colorectal cancer Disclaimer I do not have any financial conflicts to disclose. I will not be promoting any service or product. This presentation is not meant to offer medical advice and is not intended to establish a standard

More information

Update on New Perspectives in Endocrine-Sensitive Breast Cancer. James R. Waisman, MD

Update on New Perspectives in Endocrine-Sensitive Breast Cancer. James R. Waisman, MD Update on New Perspectives in Endocrine-Sensitive Breast Cancer James R. Waisman, MD Nothing to disclose DISCLOSURE TAILORx Oncotype Recurrence Score TAILORx Study Design Sparano, J Clin Oncol 2008;26:721-728

More information

ESMO 2017, Madrid, Spain Dr. Loredana Vecchione Charite Comprehensive Cancer Center, Berlin HIGHLIGHTS ON CANCERS OF THE UPPER GI TRACT

ESMO 2017, Madrid, Spain Dr. Loredana Vecchione Charite Comprehensive Cancer Center, Berlin HIGHLIGHTS ON CANCERS OF THE UPPER GI TRACT ESMO 2017, Madrid, Spain Dr. Loredana Vecchione Charite Comprehensive Cancer Center, Berlin HIGHLIGHTS ON CANCERS OF THE UPPER GI TRACT DOCETAXEL, OXALIPLATIN AND FLUOROURACIL/LEUCOVORIN (FLOT) FOR RESECTABLE

More information

Update 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 Update in the treatment of Her2- overexpressing breast cancers Fabrice ANDRE Institut Gustave Roussy Villejuif, France Questions Should tumors

More information

Metastatic Breast Cancer What is new? Subtypes and variation?

Metastatic Breast Cancer What is new? Subtypes and variation? Metastatic Breast Cancer What is new? Subtypes and variation? Anne Blaes, MD, MS University of Minnesota, Division of Hematology/Oncology Director, Adult Cancer Survivor Program Current estimates for metastatic

More information

Targeting the Oncogenic Pathway as Opposed to the Primary Tumor Site: HER2 as an Example

Targeting the Oncogenic Pathway as Opposed to the Primary Tumor Site: HER2 as an Example Targeting the Oncogenic Pathway as Opposed to the Primary Tumor Site: HER2 as an Example Dennis J Slamon, MD, PhD Professor of Medicine Chief, Division of Hematology/Oncology; Director of Clinical/Translational

More information

Life Sciences Consortium Task Force Report to The National Cancer Policy Forum Workshop

Life Sciences Consortium Task Force Report to The National Cancer Policy Forum Workshop Life Sciences Consortium Task Force Report to The National Cancer Policy Forum Workshop Gregory A. Curt, MD, Chair U.S. Medical Science Lead, Emerging Products AstraZeneca -Oncology CEO Roundtable-I May

More information

T he HER2/neu type 1 tyrosine kinase growth factor

T he HER2/neu type 1 tyrosine kinase growth factor 710 ORIGINAL ARTICLE HER2 amplification status in breast cancer: a comparison between immunohistochemical staining and fluorescence in situ hybridisation using manual and automated quantitative image analysis

More information

Quality & Quantity of life in oncology What the CT doesn t tell us. Baby boomers have gone grey!

Quality & Quantity of life in oncology What the CT doesn t tell us. Baby boomers have gone grey! Quality & Quantity of life in oncology What the CT doesn t tell us Peter Harper Guys Hospital, London UK Baby boomers have gone grey! 57 % of patients with cancer are over 65 Number of people over 65 yrs

More information

Role of Primary Resection for Patients with Oligometastatic Disease

Role of Primary Resection for Patients with Oligometastatic Disease GBCC 2018, April 6, Songdo ConvensiA, Incheon, Korea Panel Discussion 4, How Can We Better Treat Patients with Metastatic Disease? Role of Primary Resection for Patients with Oligometastatic Disease Tadahiko

More information

2 nd line Therapy and Beyond NSCLC. Alan Sandler, M.D. Oregon Health & Science University

2 nd line Therapy and Beyond NSCLC. Alan Sandler, M.D. Oregon Health & Science University 2 nd line Therapy and Beyond NSCLC Alan Sandler, M.D. Oregon Health & Science University Treatment options for advanced or metastatic (stage IIIb/IV) NSCLC Suitable for chemotherapy Diagnosis Unsuitable/unwilling

More information

MEDICAL POLICY. Proprietary Information of Excellus Health Plan, Inc. A nonprofit independent licensee of the BlueCross BlueShield Association

MEDICAL POLICY. Proprietary Information of Excellus Health Plan, Inc. A nonprofit independent licensee of the BlueCross BlueShield Association MEDICAL POLICY SUBJECT: HER-2 TESTING IN INVASIVE BREAST OR PAGE: 1 OF: 7 If a product excludes coverage for a service, it is not covered, and medical policy criteria do not apply. If a commercial product,

More information

Recent advances in the management of metastatic breast cancer in older adults

Recent advances in the management of metastatic breast cancer in older adults Recent advances in the management of metastatic breast cancer in older adults Laura Biganzoli Medical Oncology Dept New Hospital of Prato Istituto Toscano Tumori Italy Important recent advances in the

More information

Optimizing 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 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 information

HER2 FISH pharmdx TM Interpretation Guide - Breast Cancer

HER2 FISH pharmdx TM Interpretation Guide - Breast Cancer P A T H O L O G Y HER2 FISH pharmdx TM Interpretation Guide - Breast Cancer For In Vitro Diagnostic Use FDA approved as an aid in the assessment of patients for whom Herceptin TM (trastuzumab) treatment

More information

Predicting outcome in metastatic breast cancer

Predicting outcome in metastatic breast cancer Predicting outcome in metastatic breast cancer Aleix Prat, MD, PhD Medical Oncology Department Translational Genomics and Targeted Therapeutics in Solid Tumors Monday, 15 th January, Manchester, UK Disclosures

More information

Three Hours Thirty Minutes

Three Hours Thirty Minutes INTERPRETATION HER2 IQFISH pharmdx TM Interpretation Guide Three Hours Thirty Minutes it s about time Breast carcinoma (FFPE) stained with HER2 IQFISH pharmdx Gastric cancer (FFPE) stained with HER2 IQFISH

More information

Non-Anthracycline Adjuvant Therapy: When to Use?

Non-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 information

Emerging Agents in HER2-positive Disease. Mary Cianfrocca, DO Director, Breast Oncology Program Banner MD Anderson Cancer Center Gilbert, AZ

Emerging Agents in HER2-positive Disease. Mary Cianfrocca, DO Director, Breast Oncology Program Banner MD Anderson Cancer Center Gilbert, AZ Emerging Agents in HER2-positive Disease Mary Cianfrocca, DO Director, Breast Oncology Program Banner MD Anderson Cancer Center Gilbert, AZ Signal Transduction by the HER Family and Potential Mechanisms

More information

IRESSA (Gefitinib) The Journey. Anne De Bock Portfolio Leader, Oncology/Infection European Regulatory Affairs AstraZeneca

IRESSA (Gefitinib) The Journey. Anne De Bock Portfolio Leader, Oncology/Infection European Regulatory Affairs AstraZeneca IRESSA (Gefitinib) The Journey Anne De Bock Portfolio Leader, Oncology/Infection European Regulatory Affairs AstraZeneca Overview The Drug The Biomarker and Clinical Trials Sampling Lessons Learned The

More information

Estimating and explaining survival time in metastatic breast cancer

Estimating and explaining survival time in metastatic breast cancer Estimating and explaining survival time in metastatic breast cancer Dr Belinda Kiely Medical Oncologist Concord and Campbelltown Hospitals NHMRC Clinical Trials Centre, University of Sydney Clinic this

More information

A Study to Evaluate the Effect of Neoadjuvant Chemotherapy on Hormonal and Her-2 Receptor Status in Carcinoma Breast

A Study to Evaluate the Effect of Neoadjuvant Chemotherapy on Hormonal and Her-2 Receptor Status in Carcinoma Breast Original Research Article A Study to Evaluate the Effect of Neoadjuvant Chemotherapy on Hormonal and Her-2 Receptor Status in Carcinoma Breast E. Rajesh Goud 1, M. Muralidhar 2*, M. Srinivasulu 3 1Senior

More information

First phase III data on Roche s TECENTRIQ (atezolizumab) to feature at the 2016 European Society for Medical Oncology (ESMO) Congress

First phase III data on Roche s TECENTRIQ (atezolizumab) to feature at the 2016 European Society for Medical Oncology (ESMO) Congress Media Release Basel, 03 October 2016 First phase III data on Roche s TECENTRIQ (atezolizumab) to feature at the 2016 European Society for Medical Oncology (ESMO) Congress Superiority results from the phase

More information

1.5. Research Areas Treatment Selection

1.5. Research Areas Treatment Selection 1.5. Research Areas Cancer biomarker research embraces many areas of study, including tumorigenesis, metastasis, clinical trial and surrogate endpoints, cell isolation, target identification, drug resistance,

More information

Expanding Therapeutic Strategies for HER2-Positive Metastatic Breast Cancer

Expanding Therapeutic Strategies for HER2-Positive Metastatic Breast Cancer Expanding Therapeutic Strategies for HER2-Positive Metastatic Breast Cancer Sara A. Hurvitz, MD, FACP Associate Professor of Medicine University of California Los Angeles Los Angeles, California Trastuzumab

More information