Medicina de precisión en cáncer de ovario: Determinación de BRCA germinal y somático

Size: px
Start display at page:

Download "Medicina de precisión en cáncer de ovario: Determinación de BRCA germinal y somático"

Transcription

1 Medicina de precisión en cáncer de ovario: Determinación de BRCA germinal y somático Dra. Cristina Martin Lorente Hospital de la Santa Creu i Sant Pau. Barcelona

2 Introduction Ovarian cancer is the fifth leading cause of cancer death in women in developed countries. Estimated incidence of 225,000 women and 140,000 deaths per year worldwide Optimal surgery and platinum-based chemotherapy are the mainstay of front-line treatment but about 80% will relapse Up to 15% of epithelial OC cases are familial. Inherited mutations in BRCA1/2 account for the majority of familial OC with an increased lifetime risk of developing OC 40-60% BRCA1 and 11-30% BRCA2 Globocan Ford D et al Am J Hum Genet National Cancer Institute Ford D et al Am J Hum Genet 1998

3 Ovarian Cancer (OC): Multiples Diseases Different types with different behaviour Most Common High grade serous ovarian cancer (HGSOC) HGSOC: Associated with characteristics of genomic instability (TP53) and homologous recombination deficiency (BRCA)

4 Defining BRCAness Phenotype Ovarian cancers in women with BRCA1/2 germline mutations are characterized by an improved response to platinum-based chemotherapy at first and subsequent relapses and better outcomes (PFS, OS) Tan D JCO 2008; Fong FC JCO 2010; Audeh MW Lancet 2010; Ledermann J Lancet 2014; Fong FC NEJM 2009

5 Defining BRCAness Phenotype BRCA1/2 germline mutated populations have also shown exceptional sensitivity to PARP inhibitors (PARPi) Tan D JCO 2008; Fong FC JCO 2010; Audeh MW Lancet 2010; Ledermann J Lancet 2014; Fong FC NEJM 2009

6 Use BRCA deficiency for treatment Olaparib Rucaparib Veliparib Niraparib BMN-673 Tewari Clin Cancer Res 2015

7 Targeting BRCA in Ovarian Cancer: An approach for personalizing management of OC

8 PARP inhibitors in clinical trials

9 Response by BRCA status: ORR 41% with BRCAm vs 24% BRCAwt Gelmon et al. Lancet Oncol 2011

10 Study 19: To assess the efficacy and safety of oral Olaparib as maintenance treatment A randomised, double-blind, placebo-controlled Phase II maintenance study 265 patients in 82 investigational sites in 16 countries Patients: Platinum-sensitive high-grade serous ovarian cancer 2 previous platinum regimens Last chemotherapy was platinumbased, to which they had a maintained PR or CR prior to enrolment Olaparib 400 mg po bid Randomised 1:1 Placebo po bid Treatment until disease progression Primary end point: Progression free survival Ledermann J et al. N Engl J Med 2012

11 Olaparib met the primary endpoint of improving PFS in the OVERALL study population Ledermann J et al. N Engl J Med 2012

12 More than 50% patients had a known deleterious BRCAm (Pre-planned BRCA testing) Patients with a known BRCA status increased from 98 (37%) to 254 (95.8%) out of 265: 136 (51.3%) patients had a known deleterious BRCAm (BRCAm dataset) 118 (44.5%) patients were defined as BRCA1/2 wild type for this analysis 11 (4.2%) patients had neither a tumour nor a germline result available Ledermann J et al. N Engl J Med 2012

13 Proportion of patients progression-free Olaparib significantly prolonged PFS in platinum-sensitive relapsed HGSOC Patients with a BRCA mutation receive greater treatment benefit Non-mutation carriers may also benefit from olaparib treatment Median PFS, months BRCAm (n=136) BRCAwt (n=118) Olaparib Placebo Olaparib Placebo HR=0.18 HR=0.53 P< P= Olaparib BRCAm Placebo BRCAm Olaparib BRCAwt Placebo BRCAwt Time from randomization (months) Ledermann et al. N Eng J Med Ledermann et al. Lancet Oncol 2014

14 BRCA germline mutations BRCA somatic mutations BRCAness Phenotype Similar to germline BRCAm, PFS was longer in somatic BRCAm population compared with wildtype Germline or somatic HR mutations was highly predictive of primary platinum and PARPi sensitivity and improved overall survival Hennessy JCO 2010/ Pennington CCR 2014

15 WHO TO TEST? In the past we used to refer patients to genetic counseling based on their family history and personal history Nowadays we have a broaden vision of the disease which supports that this policy is not accurate enough

16 Frequency of BRCA1/2 mutations in women with OC is unclear (3-27%) women enrolled onto a population-based case-control study were screened Germ-line mutations were found in 14.4% of patients (22.6% HGSOC; 8.4% endometrioid; 6%CC; 0% carcinosarcoma) 44% had not reported family history of breast or OC BRCAm was associated with better outcomes (RR, PFS, OS) Conclusions: BRCA status has a major influence on survival, treatment outcomes and treatment selection and SHOULD BE OFFERED TO ALL WOMEN DIAGNOSED WITH NON-MUCINOUS OC REGARDLESS OF FAMILY HISTORY Alsop K JCO 2012

17 WHO TO TEST?

18 What about SOMATIC Testing? Ovarian cancer in women with BRCA somatic mutation (BRCAg wt) is also characterized by an improved response to platinum-based chemotherapy and PARP inhibitors and by better outcomes with longer PFS and improved OS Olaparib approved by EMA as first-in-class treatment for advanced BRCA-MUTATED (germline and somatic) ovarian cancer (January 2015) BRCA somatic mutation testing expands the number of patients who would benefit from personalized medicine

19 WHEN TO TEST? Initial diagnosis preferable PRO Access to pathology Biomarker of response to platinum-based chemotherapy Prognostic factor Likely PARPi will be approved in front-line setting Genetic counselling CON: Evidence supporting temporal heterogeneity in OC

20 WHICH ONE FIRST? GERMLINE TESTING Well-established Lymphocyte DNA more reliable Need for genetic counselling Wildtype, still need to test somatic mutation SOMATIC TESTING Streamline testing Less need for genetic counselling Require good quality of DNA Technical Considerations

21 BRCAness Phenotype BRCA germline mutations BRCA somatic mutations (Hennessy JCO 2010) Other Homologous Recombination DNA repair defects (Kristeleit ECC Pennington CCR 2014) Levine. Nature 2011

22 HRD Assays: Lines of Research Next-generation sequencing assays. Gene expression analysis. BROCA: analysis of mutations of key HR genes (BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK1, CHEK2, FAM175A, MRE11A, NBN, PALB2, RAD51C, RAD51D). 60-genes signature of BRCAness High correlation with response to platinum-based therapy an overall survival. NOT VALIDATED. Functional ex-vivo assays: RAD51 nuclear foci formation by immunofluorescence or other DNA repair complexes by immunohistochemistry PRO: Dynamic and functional biomarker CON: Requires fresh tissue. Reproducibility. Genome scars. ARIEL 2. Rucaparib and genomic LOH assay (Foundation Medicine) NOVA trial. Niraparib and HRD score (mychoice HRDTM Myriad)

23 HRD Assays: ARIEL 2 Different mechanisms can lead to HRD with the final result of genomic instability and large areas of genomic scaring (uniparental deletions) HRD causes genome wide LOH that can be measured by NGS TCGA and AOCS developed LOH cutoff based on overall survival to identify patients with HGSOC with BRCA-like signature McNeish IA ASCO TCGA Nature Wang Clin Cancer Res 2012

24 CONCLUSIONS BRCAness profile is now beyond mutations in BRCA germline This profile predicts platinum and PARPi sensitivity and better clinical outcomes BRCA testing in the germline and in the tumor expands up to 20% the number of patients who would benefit from targeted treatments Ideally, patients should be tested at diagnosis The validation of HRD assays and multiple gene sequencing panels to guide treatment selection is under evaluation Clinical trials on-going will offer additional insight

25 GRACIAS

26 ARIEL 2 (Part 1): Phase 2 trial to prospectively identify OC responders to rucaparib using tumor genetic analysis Kristeleit et al ECCO 2015

27 Efficacy Analysis ARIEL 2 (Part 1) PFS in tbrca mut and tbrcalike vs. biomarker negative patients Duration of response in tbrca mut and tbrca-like vs. biomarker negative patients Kristeleit et al ECCO 2015

28 ENGOT-OV16/NOVA Phase 3 randomized double-blind of maintenance with niraparib vs. placebo in patients with platinum sensitive OC Mirza ESMO 2016

29 HRD Assays: HRD Score Tesaro. WorldCDx 2015

30 HRD Assays: HRD Score The HRD test does not identify origin of mutation (germline or somatic) It is based on sequencing ~54,000 SNP regions of the genome and the BRCA1/2 genes (mychoice HRDTM Myriad) Tesaro. WorldCDx 2015

31 NOVA Trial: PFS by gbrca status gbrca Mutated gbrca Wild Type Mirza ESMO 2016

32 NOVA Trial: Exploratory Analysis PFS in gbrcawt Subgroups Mirza ESMO 2016

33 Conclusions To identify potential biomarker drivers of efficacy is urgently needed The presence of HRD may be a valid strategy for selection for DNA repair inhibitors as PARPi The actual HRD assays do not seem to be accurate enough to identify patients who don t benefit from PARPi

34

PARP Inhibitors: Patients Selection. Dr. Cristina Martin Lorente Hospital de la Santa Creu i Sant Pau Formigal, June 23th 2016

PARP Inhibitors: Patients Selection. Dr. Cristina Martin Lorente Hospital de la Santa Creu i Sant Pau Formigal, June 23th 2016 PARP Inhibitors: Patients Selection Dr. Cristina Martin Lorente Hospital de la Santa Creu i Sant Pau Formigal, June 23th 2016 OVARIAN CANCER (OC): MULTIPLES DISEASES Different types with different behaviour

More information

Update on PARP inhibitors: opportunities and challenges in cancer therapy

Update on PARP inhibitors: opportunities and challenges in cancer therapy Update on PARP inhibitors: opportunities and challenges in cancer therapy Vanda Salutari Unità di Ginecologia Oncologica Fondazione Policlinico Universitario A. Gemelli vanda.salutari@policlinicogemelli.it

More information

Inhibidores de PARP en cáncer de ovario

Inhibidores de PARP en cáncer de ovario Inhibidores de PARP en cáncer de ovario Ma Pilar Barretina Ginesta Servicio Oncología Médica Hospital Universitari Dr. J. Trueta Institut Català d Oncologia Coordinación científica: Dr. Fernando Rivera

More information

A New String to the Bow in the Treatment of Advanced Ovarian Cancer Bradley J. Monk, MD, FACS, FACOG

A New String to the Bow in the Treatment of Advanced Ovarian Cancer Bradley J. Monk, MD, FACS, FACOG A New String to the Bow in the Treatment of Advanced Ovarian Cancer Bradley J. Monk, MD, FACS, FACOG Arizona Oncology (US Oncology Network) Professor, Gynecologic Oncology University of Arizona and Creighton

More information

Ricombinazione omologa nel carcinoma ovarico: BRCA e oltre. F. Raspagliesi MD

Ricombinazione omologa nel carcinoma ovarico: BRCA e oltre. F. Raspagliesi MD Ricombinazione omologa nel carcinoma ovarico: BRCA e oltre F. Raspagliesi MD raspagliesi@istitutotumori.mi.it BRCA molecular signature in ovarian cancer In a pooled analysis of 26 observational studies

More information

Genetic Testing For Ovarian Cancer: When, How And Who? Judith Balmaña, MD, PhD University Hospital Vall d Hebron Barcelona, Spain

Genetic Testing For Ovarian Cancer: When, How And Who? Judith Balmaña, MD, PhD University Hospital Vall d Hebron Barcelona, Spain Genetic Testing For Ovarian Cancer: When, How And Who? Judith Balmaña, MD, PhD University Hospital Vall d Hebron Barcelona, Spain Why Would We Consider Genetic Testing in Patients With Ovarian Cancer?

More information

Importanza del test genetico nel carcinoma mammario ed ovarico

Importanza del test genetico nel carcinoma mammario ed ovarico Importanza del test genetico nel carcinoma mammario ed ovarico Lorena Incorvaia Azienda Ospedaliera Universitaria Policlinco «P.Giaccone» Palermo UOC Oncologia Medica Ovarian Cancer Breast Cancer The range

More information

Virtual Journal Club. Ovarian Cancer. Reference Slides. Platinum-Sensitive Recurrent Ovarian Cancer: Making the Most of Emerging Targeted Therapies

Virtual Journal Club. Ovarian Cancer. Reference Slides. Platinum-Sensitive Recurrent Ovarian Cancer: Making the Most of Emerging Targeted Therapies Virtual Journal Club Ovarian Cancer Reference Slides Platinum-Sensitive Recurrent Ovarian Cancer: Making the Most of Emerging Targeted Therapies Mansoor R. Mirza, MD Copenhagen University Hospital Rigshospitalet

More information

Dr. Josep M. Del Campo Clínica Diagonal. Barcelona

Dr. Josep M. Del Campo Clínica Diagonal. Barcelona Dr. Josep M. Del Campo Clínica Diagonal. Barcelona Nuevas Oportunidades en Cáncer de Ovario Cancer de Ovario: Es una enfermedad única? Cáncer de Ovario: Tratamiento actual Tratamiento inicial: sin cambios

More information

PARP inhibitors for breast cancer

PARP inhibitors for breast cancer PARP inhibitors for breast cancer Mark Robson, MD Memorial Sloan Kettering Cancer Center Agenda Mechanism of action Clinical studies Resistance mechanisms Future directions Poly (ADP-ribose) Polymerases

More information

Practical Guidance and Strategies for PARP Inhibition. Nicoletta Colombo, MD University of Milan-Bicocca European Institute of Oncology Milan, Italy

Practical Guidance and Strategies for PARP Inhibition. Nicoletta Colombo, MD University of Milan-Bicocca European Institute of Oncology Milan, Italy Practical Guidance and Strategies for PARP Inhibition Nicoletta Colombo, MD University of Milan-Bicocca European Institute of Oncology Milan, Italy Clinical Data Maintenance therapy : BRCA-mutated or all

More information

ESMO SUMMIT AFRICA. Latest evidence and current standard of care in advanced ovarian cancer. C.Sessa. Cape Town February 2018

ESMO SUMMIT AFRICA. Latest evidence and current standard of care in advanced ovarian cancer. C.Sessa. Cape Town February 2018 ESMO SUMMIT AFRICA Latest evidence and current standard of care in advanced ovarian cancer C.Sessa IOSI, Bellinzona, CH Cape Town 14-16 February 2018 CONFLICT OF INTEREST DISCLOSURE None Ovarian carcinoma

More information

2015 EUROPEAN CANCER CONGRESS

2015 EUROPEAN CANCER CONGRESS 2015 EUROPEAN CANCER CONGRESS 25-29 September 2015 Vienna, Austria SUMMARY The European Cancer Congress (ECC 2015) combined the 40th European Society for Medical Oncology (ESMO) congress with the 18th

More information

Evaluation of BRCA1/2 and homologous recombination defects in ovarian cancer and impact on clinical outcomes

Evaluation of BRCA1/2 and homologous recombination defects in ovarian cancer and impact on clinical outcomes Evaluation of BRCA1/2 and homologous recombination defects in ovarian cancer and impact on clinical outcomes Melinda S. Yates, PhD Department of Gynecologic Oncology & Reproductive Medicine University

More information

Myriad Genetics mychoice HRD Update 06/30/2016

Myriad Genetics mychoice HRD Update 06/30/2016 Myriad Genetics mychoice HRD Update 06/30/2016 1 Forward Looking Statements Some of the information presented here today may contain projections or other forward-looking statements regarding future events

More information

TREATMENT FOR RELAPSING PLATINUM SENSITIVE EPITHELIAL OVARIAN CANCER

TREATMENT FOR RELAPSING PLATINUM SENSITIVE EPITHELIAL OVARIAN CANCER TREATMENT FOR RELAPSING PLATINUM SENSITIVE EPITHELIAL OVARIAN CANCER Sandro Pignata, MD, PhD Sabrina Chiara Cecere, MD Uro-Gynecological Department, Division of Medical Oncology, IRCCS National Cancer

More information

Nuevas estrategias de tratamiento en tumores con mutaciones de BRCA

Nuevas estrategias de tratamiento en tumores con mutaciones de BRCA Nuevas estrategias de tratamiento en tumores con mutaciones de BRCA Emilio Alba UGCI Oncología Hospital Universitario Regional y Virgen de la Victoria Facultad de Medicina. Málaga IBIMA ÍNDICE DE LA PRESENTACIÓN

More information

33 rd Annual J.P. Morgan Healthcare Conference. January 2015

33 rd Annual J.P. Morgan Healthcare Conference. January 2015 33 rd Annual J.P. Morgan Healthcare Conference January 2015 Forward-looking Statements This presentation contains forward-looking statements, which express the current beliefs and expectations of management.

More information

The OReO Study. Study design & Protocol Study design Key Inclusion criteria Patient population Recruitment and retention tools

The OReO Study. Study design & Protocol Study design Key Inclusion criteria Patient population Recruitment and retention tools The OReO Study A Phase IIIb, Randomised, Double-blind, Placebo-controlled, multi-centre Study of Olaparib Maintenance Re-treatment in Patients with Epithelial Ovarian Cancer Previously treated with a and

More information

Brian T Burgess, DO, PhD, GYN Oncology Fellow Rachel W. Miller, MD, GYN Oncology

Brian T Burgess, DO, PhD, GYN Oncology Fellow Rachel W. Miller, MD, GYN Oncology Brian T Burgess, DO, PhD, GYN Oncology Fellow Rachel W. Miller, MD, GYN Oncology Epithelial Ovarian Cancer - Standard Current Treatment: Surgery with De-bulking + Platinum-Taxane based Chemotherapy - No

More information

Update on PARP inhibitors

Update on PARP inhibitors Professor of Medicine Harvard Medical School Boston MA Update on PARP inhibitors Ursula Matulonis, M.D. Chief, Division of Gynecologic Oncology Brock-Wilson Family Chair Dana-Farber Cancer Institute History

More information

Overview and future horizons of PARP inhibitors in BRCAassociated. Judith Balmaña

Overview and future horizons of PARP inhibitors in BRCAassociated. Judith Balmaña Overview and future horizons of PARP inhibitors in BRCAassociated breast cancer Judith Balmaña PARP inhibitors: Mechanism of action Clinical development: Monotherapy In combination with chemotherapy Ongoing

More information

Clinical Development of Rucaparib

Clinical Development of Rucaparib Clinical Development of Rucaparib Rucaparib is an investigational product and not approved by any health authority. Conclusions about efficacy and safety cannot be made Development of HRD/LOH Signature

More information

The Role of PARP Inhibitors in Ovarian Cancer: An Emerging Picture

The Role of PARP Inhibitors in Ovarian Cancer: An Emerging Picture The Role of PARP Inhibitors in Ovarian Cancer: An Emerging Picture This satellite symposium took place on 10 th September 2017 as part of the European Society for Medical Oncology (ESMO) Congress in Madrid,

More information

Ovarian Cancer: It s Personal

Ovarian Cancer: It s Personal Ovarian Cancer: It s Personal Review ovarian cancer: Incidence, origin, and management Discuss genetic testing: Who, why and what? Review current treatments for ovarian cancer Enhance understanding of

More information

Optimizing DNA Damage Response- Targeting Therapies: Focus on Genetic Testing and Counseling

Optimizing DNA Damage Response- Targeting Therapies: Focus on Genetic Testing and Counseling Disclaimer This slide deck in its original and unaltered format is for educational purposes and is current as of May 2017. The content and views presented in this educational activity are those of the

More information

DNA Damage Response analyst science event

DNA Damage Response analyst science event DNA Damage Response analyst science event Mene Pangalos, EVP, Innovative Medicines & Early Development and Business Development Klaus Edvardsen, Vice President, Oncology Clinical, Global Medicines Development

More information

Biomarker for Response and Resistance in Ovarian Cancer

Biomarker for Response and Resistance in Ovarian Cancer 2016 대한부인종양학회제 31 차춘계학술대회 New Trends in Translational Research Biomarker for Response and Resistance in Ovarian Cancer Shin-Wha Lee, M.D., Ph.D. Department of Obstetrics and Gynecology ASAN Medical Center

More information

Drug Niraparib Olaparib

Drug Niraparib Olaparib Dear NCCN Value Pathway Committee, We are making this submission to provide information that we believe is relevant for developing NCCN Categories of Preference for the use of PARP inhibitors in recurrent

More information

PARP inibitori nel trattamento del carcinoma mammario metastatico: recenti successi e prospettive future.

PARP inibitori nel trattamento del carcinoma mammario metastatico: recenti successi e prospettive future. PARP inibitori nel trattamento del carcinoma mammario metastatico: recenti successi e prospettive future. Dr.ssa Angela Toss Centro Oncologico Modenese Università di Modena e Reggio Emilia MECHANISMS OF

More information

ESMO PRECEPTORSHIP IN IMMUNO-ONCOLOGY

ESMO PRECEPTORSHIP IN IMMUNO-ONCOLOGY ESMO PRECEPTORSHIP IN IMMUNO-ONCOLOGY LUGANO, MAY 4-5, 2018 Clinical development in ovarian cancer C. Sessa, CH CONTENT Rationale for immunotherapy in ovarian cancer Clinical data with single agent immune

More information

PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland

PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland AWARD NUMBER: W81XWH-13-1-0421 TITLE: The Fanconi Anemia BRCA Pathway as a Predictor of Benefit from Bevacizumab in a Large Phase III Clinical Trial in Ovarian Cancer PRINCIPAL INVESTIGATOR: Elizabeth

More information

Ovarian Cancer: New insights into biology and treatment

Ovarian Cancer: New insights into biology and treatment Ovarian Cancer: New insights into biology and treatment 2018 Master Class Course Ursula A. Matulonis, MD Director, Gynecologic Oncology Brock-Wilson Family Chair Dana-Farber Cancer Institute Professor

More information

Germline Testing for Hereditary Cancer with Multigene Panel

Germline Testing for Hereditary Cancer with Multigene Panel Germline Testing for Hereditary Cancer with Multigene Panel Po-Han Lin, MD Department of Medical Genetics National Taiwan University Hospital 2017-04-20 Disclosure No relevant financial relationships with

More information

Genetic Testing Today: What Genes Can Tell Us. Living Beyond Breast Cancer Conference Kara N. Maxwell, MD, PhD University of Pennsylvania

Genetic Testing Today: What Genes Can Tell Us. Living Beyond Breast Cancer Conference Kara N. Maxwell, MD, PhD University of Pennsylvania Genetic Testing Today: What Genes Can Tell Us Living Beyond Breast Cancer Conference Kara N. Maxwell, MD, PhD University of Pennsylvania Overview of talk PART 1: Overview of Genetics PART 2: BRCA1/2 PART

More information

Clinical Data With PARP Inhibitors in Ovarian Cancer

Clinical Data With PARP Inhibitors in Ovarian Cancer Clinical Data With PARP Inhibitors in Ovarian Cancer Thomas J. Herzog, MD, FACOG, FACS Paul & Carolyn Flory Professor Clinical Director, University of CincinnaD Cancer InsDtute CincinnaD, OH Clinical Data

More information

GOG-172: Survival Outcomes

GOG-172: Survival Outcomes CHEMOTHERAPY GOG-172: Survival Outcomes Progression-Free Survival Overall Survival Proportion Progression-Free 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Rx Group IV IP PF Failed Total 50 160 210 63 142

More information

Key Recommendations. Gynecologic management of women with inherited risk of gynecologic cancer

Key Recommendations. Gynecologic management of women with inherited risk of gynecologic cancer Gynecologic management of women with inherited risk of gynecologic cancer C. Bethan Powell MD Kaiser Permanente Northern California Gynecologic Oncology Program Lead, Kaiser Permanente Northern California

More information

Learning Objectives. Page 1

Learning Objectives. Page 1 Learning Objectives 1. Outline the role of the DNA damage response (DDR) pathway in tumor suppression and describe how mutations in DDR genes lead to tumor proliferation. 2. Explore recent advances in

More information

From Research to Practice: What s New in Gynecologic Cancers?

From Research to Practice: What s New in Gynecologic Cancers? From Research to Practice: What s New in Gynecologic Cancers? David Warshal, M.D. Head, Division of Gynecologic Oncology MD Anderson Cooper Cancer Institute Associate Professor of Obstetrics and Gynecology

More information

Progress Update June 2017 Lay Summary Funding: $6,000,000 Grant Funded: July 2015 Dream Team Members Dream Team Leader:

Progress Update June 2017 Lay Summary Funding: $6,000,000 Grant Funded: July 2015 Dream Team Members Dream Team Leader: SU2C -Ovarian Cancer Research Fund Alliance-National Ovarian Cancer Coalition Dream Team Translational Research Grant: DNA Repair Therapies for Ovarian Cancer AND SU2C Catalyst Merck-Supported Supplemental

More information

Genetics & Precision Medicine Cancer Care

Genetics & Precision Medicine Cancer Care Genetics & Precision Medicine Cancer Care Johnathan M. Lancaster, MD PhD Chief Medical Officer Myriad Genetics Copyright 2015 Myriad Genetics, Inc., all rights reserved. www.myriad.com. Precision Medicine

More information

FDA Companion Diagnostic Testing and Implications for Pharmacy and Medical Directors

FDA Companion Diagnostic Testing and Implications for Pharmacy and Medical Directors FDA Companion Diagnostic Testing and Implications for Pharmacy and Medical Directors Diana Brixner, PhD, RPh, FAMCP Professor, University of Utah Health Sciences Executive Director, Pharmacotherapy Outcomes

More information

Advanced Ovarian Carcinoma

Advanced Ovarian Carcinoma Advanced Ovarian Carcinoma What is our standard of care? IV carbo/taxol IP platinum/taxane (what regimen?) IV carbo/taxol/bevacizumab + 12 months of Bev IV carbo + dose dense taxol Controversy between

More information

Moderator: Paula J. Anastasia RN, MN, AOCN Gyn-Onc Clinical Nurse Specialist Cedars-Sinai Medical Center Los Angeles, CA

Moderator: Paula J. Anastasia RN, MN, AOCN Gyn-Onc Clinical Nurse Specialist Cedars-Sinai Medical Center Los Angeles, CA Disclaimer This slide deck in its original and unaltered format is for educational purposes and is current as of May 2017. The content and views presented in this educational activity are those of the

More information

GYNplus: A Genetic Test for Hereditary Ovarian and/or Uterine Cancer

GYNplus: A Genetic Test for Hereditary Ovarian and/or Uterine Cancer GYNplus: A Genetic Test for Hereditary Ovarian and/or Uterine Cancer Causes of Hereditary Ovarian and Uterine Cancer uterine cancer ovarian cancer Sporadic 75-90% Sporadic 70-80% Hereditary, 5% Lynch syndrome

More information

Triple-Negative Breast Cancer Time to Slice and Dice? Carsten Denkert, MD Charité University Hospital Berlin, Germany

Triple-Negative Breast Cancer Time to Slice and Dice? Carsten Denkert, MD Charité University Hospital Berlin, Germany Triple-Negative Breast Cancer Time to Slice and Dice? Carsten Denkert, MD Charité University Hospital Berlin, Germany Triple-Negative Breast Cancer (TNBC) 2018 Presentation Outline The molecular heterogeneity

More information

Disclosure. Gynecologic Cancer Genetics. Audience response. Audience response. What was the result? 47%

Disclosure. Gynecologic Cancer Genetics. Audience response. Audience response. What was the result? 47% Disclosure Cancer Genetics I have served as a moderator for an advisory board to Genentech Lee-may Chen, M.D. Professor Department of Obstetrics, Gynecology, & Reproductive Sciences UCSF Obstetrics and

More information

Triple-Negative Breast Cancer

Triple-Negative Breast Cancer June 2017 Triple-Negative Breast Cancer Amir Sonnenblick, MD, PhD Sharett institute of oncology Hadassah-Hebrew university medical center, Jerusalem, Israel This presentation is the intellectual property

More information

SOLO-1. Dott.ssa Elisabetta Sanna U.O.C. Ginecologia Oncologica- AOB Cagliari Direttore: Dott. Antonio Macciò

SOLO-1. Dott.ssa Elisabetta Sanna U.O.C. Ginecologia Oncologica- AOB Cagliari Direttore: Dott. Antonio Macciò SOLO-1 maintenance therapy in patients with newly diagnosed advanced ovarian cancer following platinum-based chemotherapy Dott.ssa Elisabetta Sanna U.O.C. Ginecologia Oncologica- AOB Cagliari Direttore:

More information

PARP inhibitors in platinum-sensitive high-grade serous ovarian cancer

PARP inhibitors in platinum-sensitive high-grade serous ovarian cancer Cancer Chemotherapy and Pharmacology (2018) 81:647 658 https://doi.org/10.1007/s00280-018-3532-9 REVIEW ARTICLE PARP inhibitors in platinum-sensitive high-grade serous ovarian cancer Robert D. Morgan 1,2

More information

Assessment and Management of Genetic Predisposition to Breast Cancer. Dr Munaza Ahmed Consultant Clinical Geneticist 2/7/18

Assessment and Management of Genetic Predisposition to Breast Cancer. Dr Munaza Ahmed Consultant Clinical Geneticist 2/7/18 Assessment and Management of Genetic Predisposition to Breast Cancer Dr Munaza Ahmed Consultant Clinical Geneticist 2/7/18 Overview The role of the Cancer Genetics team NICE guidelines for Familial Breast

More information

2/21/2016. Cancer Precision Medicine: A Primer. Ovarian Cancer Statistics and Standard of Care in 2015 OUTLINE. Background

2/21/2016. Cancer Precision Medicine: A Primer. Ovarian Cancer Statistics and Standard of Care in 2015 OUTLINE. Background Cancer Precision Medicine: A Primer Rebecca C. Arend, MD Division of Gyn Oncology OUTLINE Background Where we are Where we have been Where we are going Targeted Therapy in Ovarian Cancer How to Individualized

More information

BRCAplus. genetic testing for hereditary breast cancer

BRCAplus. genetic testing for hereditary breast cancer BRCAplus genetic testing for hereditary breast cancer Developed in collaboration with Fox Chase Cancer Center and the Arcadia University Genetic Counseling Program. Causes of Hereditary Breast Cancer familial

More information

GYNplus. genetic testing for hereditary ovarian and/or uterine cancer

GYNplus. genetic testing for hereditary ovarian and/or uterine cancer GYNplus genetic testing for hereditary ovarian and/or uterine cancer What Are the Causes of Hereditary Ovarian and Uterine Cancer? uterine cancer ovarian cancer sporadic 70-80% hereditary 5% Lynch syndrome

More information

CASE STUDY. Mutation-Specific Testing: Eligibility for PARP Inhibitor Therapy Established. Introduction. Patient Profile.

CASE STUDY. Mutation-Specific Testing: Eligibility for PARP Inhibitor Therapy Established. Introduction. Patient Profile. CASE STUDY Mutation-Specific Testing: Eligibility for PARP Introduction Genetic testing is an emergent diagnostic technique that can provide specific and actionable inputs to the management of cancer therapy.

More information

WHAT IS A GENE? CHROMOSOME DNA PROTEIN. A gene is made up of DNA. It carries instructions to make proteins.

WHAT IS A GENE? CHROMOSOME DNA PROTEIN. A gene is made up of DNA. It carries instructions to make proteins. WHAT IS A GENE? CHROMOSOME E GEN DNA A gene is made up of DNA. It carries instructions to make proteins. The proteins have specific jobs that help your body work normally. PROTEIN 1 WHAT HAPPENS WHEN THERE

More information

Inhibidores de PARP Una realidad? dónde y cuando?

Inhibidores de PARP Una realidad? dónde y cuando? Inhibidores de PARP Una realidad? dónde y cuando? Alberto Ocana Hospital Universitario Albacete Centro Regional Investigaciones Biomédicas CIC-Salamanca DNA repair mechanisms DNA is continually exposed

More information

ESMO SUMMIT MIDDLE EAST 2018

ESMO SUMMIT MIDDLE EAST 2018 ESMO SUMMIT MIDDLE EAST 2018 Practice changing studies in Gynecological Cancer in 2017 Dr Susana Banerjee MBBS MA PhD FRCP Consultant Medical Oncologist and Research Lead Gynaecology Unit The Royal Marsden

More information

Clovis Oncology Announces First Quarter 2017 Operating Results. May 3, :06 PM ET

Clovis Oncology Announces First Quarter 2017 Operating Results. May 3, :06 PM ET Clovis Oncology Announces First Quarter 2017 Operating Results May 3, 2017 4:06 PM ET Strong Q1 launch quarter for Rubraca (rucaparib) in U.S. with $7M reported in net sales Clovis notified that ARIEL3

More information

Carcinoma mammario triple nega0ve Nuove acquisizioni biologiche. Giuseppe Curigliano MD PhD UNIMI & IEO

Carcinoma mammario triple nega0ve Nuove acquisizioni biologiche. Giuseppe Curigliano MD PhD UNIMI & IEO Carcinoma mammario triple nega0ve Nuove acquisizioni biologiche Giuseppe Curigliano MD PhD UNIMI & IEO Outline San Antonio Breast Cancer Symposium, December 5-9, 2017 The year of DNA Repair targe?ng Olaparib

More information

Rowan E. Miller, MD, and Jonathan A. Ledermann, MD. Introduction

Rowan E. Miller, MD, and Jonathan A. Ledermann, MD. Introduction The Status of Poly(Adenosine Diphosphate- Ribose) Polymerase (PARP) Inhibitors in Ovarian Cancer, Part 2: Extending the Scope Beyond Olaparib and BRCA1/2 Mutations Rowan E. Miller, MD, and Jonathan A.

More information

Biology Response Controversies and Advances

Biology Response Controversies and Advances Biology Response Controversies and Advances in BRCA related ovarian cancer Lessons learned and future directions Michael Friedlander The Prince of Wales Hospital and Royal Hospital for Women Sydney BREAST-CANCER

More information

PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland

PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland AWARD NUMBER: W81XWH-13-1-0421 TITLE: The Fanconi Anemia BRCA Pathway as a Predictor of Benefit from Bevacizumab in a Large Phase III Clinical Trial in Ovarian Cancer PRINCIPAL INVESTIGATOR: Elizabeth

More information

PROSTATE CANCER HORMONE THERAPY AND BEYOND. Przemyslaw Twardowski MD Professor of Oncology Department of Urologic Oncology John Wayne Cancer Institute

PROSTATE CANCER HORMONE THERAPY AND BEYOND. Przemyslaw Twardowski MD Professor of Oncology Department of Urologic Oncology John Wayne Cancer Institute PROSTATE CANCER HORMONE THERAPY AND BEYOND Przemyslaw Twardowski MD Professor of Oncology Department of Urologic Oncology John Wayne Cancer Institute Disclosures I am a Consultant for Bayer and Sanofi-Aventis

More information

Technology appraisal guidance Published: 4 July 2018 nice.org.uk/guidance/ta528

Technology appraisal guidance Published: 4 July 2018 nice.org.uk/guidance/ta528 Niraparib for maintenance treatment of relapsed, platinum-sensitive e ovarian, fallopian tube and peritoneal cancer Technology appraisal guidance Published: 4 July 2018 nice.org.uk/guidance/ta528 NICE

More information

Targeted Molecular Therapy Gynaecological Cancer Where are we now?

Targeted Molecular Therapy Gynaecological Cancer Where are we now? Targeted Molecular Therapy Gynaecological Cancer Where are we now? 0 T O M D E G R E V E S U B - S P E C I A LT Y F E L L O W G Y N A E C O L O G I C A L O N C O L O G Y U N I V E R S I T Y O F P R E T

More information

Summary... 2 GYNAECOLOGICAL CANCER Niraparib in second-line treatment for platinum sensitive recurrant ovarian cancer... 3

Summary... 2 GYNAECOLOGICAL CANCER Niraparib in second-line treatment for platinum sensitive recurrant ovarian cancer... 3 ESMO 2016 Congress 7-11 October, 2016 Copenhagen, Denmark Table of Contents Summary... 2 GYNAECOLOGICAL CANCER... 3 Niraparib in second-line treatment for platinum sensitive recurrant ovarian cancer...

More information

Modelling cancer risk predictions:clinical practice perspective.

Modelling cancer risk predictions:clinical practice perspective. Modelling cancer risk predictions:clinical practice perspective. Judith Balmaña, MD, PhD Familial Cancer Program Medical Oncology Department Hospital Vall d Hebron, VHIO Barcelona, Spain It is very difficult

More information

New Treatments for Early Ovarian Cancer. Jonathan Ledermann UCL Cancer Institute University College London

New Treatments for Early Ovarian Cancer. Jonathan Ledermann UCL Cancer Institute University College London New Treatments for Early Ovarian Cancer Jonathan Ledermann UCL Cancer Institute University College London Lucerne Oct 213 Progression-free survival in first-line trials of platinum-based chemotherapy 1998

More information

Update on Poly ADP ribose polymerase inhibition for ovarian cancer treatment

Update on Poly ADP ribose polymerase inhibition for ovarian cancer treatment DOI 10.1186/s12967-016-1027-1 Journal of Translational Medicine REVIEW Open Access Update on Poly ADP ribose polymerase inhibition for ovarian cancer treatment Anselmo Papa 1*, Davide Caruso 1, Martina

More information

Gynecologic Cancers are many diseases. Gynecologic Cancers in the Age of Precision Medicine Advances in Internal Medicine. Speaker Disclosure:

Gynecologic Cancers are many diseases. Gynecologic Cancers in the Age of Precision Medicine Advances in Internal Medicine. Speaker Disclosure: Gynecologic Cancer Care in the Age of Precision Medicine Gynecologic Cancers in the Age of Precision Medicine Advances in Internal Medicine Lee-may Chen, MD Department of Obstetrics, Gynecology & Reproductive

More information

Germline Genetic Testing for Breast Cancer Risk

Germline Genetic Testing for Breast Cancer Risk Kathmandu, Bir Hospital visit, August 2018 Germline Genetic Testing for Breast Cancer Risk Evidence-based Genetic Screening Rodney J. Scott Demography in New South Wales (total population ~ 7,000,000)

More information

Gynecologic Cancers are many diseases. Speaker Disclosure: Gynecologic Cancer Care in the Age of Precision Medicine. Controversies in Women s Health

Gynecologic Cancers are many diseases. Speaker Disclosure: Gynecologic Cancer Care in the Age of Precision Medicine. Controversies in Women s Health Gynecologic Cancer Care in the Age of Precision Medicine Gynecologic Cancers in the Age of Precision Medicine Controversies in Women s Health Lee-may Chen, MD Department of Obstetrics, Gynecology & Reproductive

More information

Cancer Risks Associated With Inherited Mutations in Ovarian Cancer Susceptibility Genes Beyond BRCA1 and BRCA2

Cancer Risks Associated With Inherited Mutations in Ovarian Cancer Susceptibility Genes Beyond BRCA1 and BRCA2 AWARD NUMBER: W81XWH-15-1-0084 TITLE: Cancer Risks Associated With Inherited Mutations in Ovarian Cancer Susceptibility Genes Beyond BRCA1 and BRCA2 PRINCIPAL INVESTIGATOR: Elizabeth Swisher CONTRACTING

More information

Targeting the DNA Damage Response: Lessons Learned and the Path Forward

Targeting the DNA Damage Response: Lessons Learned and the Path Forward Targeting the DNA Damage Response: Lessons Learned and the Path Forward Timothy A. Yap MBBS PhD MRCP BSc PgDip Associate Professor, Investigational Cancer Therapeutics and Thoracic/Head & Neck Medical

More information

Learning Objectives. Page 1

Learning Objectives. Page 1 Learning Objectives 1) Analyze the main signaling pathways and key mechanisms in DNA damage repair and how deficiencies in these pathways can lead to tumor proliferation and growth. 2) Examine the pharmacology

More information

Versus. Cancer genomics Competitive Analysis

Versus. Cancer genomics Competitive Analysis Cancer genomics Competitive Analysis Versus AGH Competitor #1 MYRIAD GENETICS, INC. Headquarters: UT, USA & Switzerland Publicly Traded Company - MYGN Founded: 1992 Company Size: 1001-5000 employees (source:

More information

Gynecologic Oncology Unit IRCCS Istituto Tumori Milano G. Maltese. Milan - Italy

Gynecologic Oncology Unit IRCCS Istituto Tumori Milano G. Maltese. Milan - Italy Gynecologic Oncology Unit IRCCS Istituto Tumori Milano G. Maltese Milan - Italy Mutations typically associated with ovarian carcinoma subtypes High-grade serous ovarian cancer TP53: encodes a protein that

More information

Summary... 2 TRANSLATIONAL RESEARCH Tumour gene expression used to direct clinical decision-making for patients with advanced cancers...

Summary... 2 TRANSLATIONAL RESEARCH Tumour gene expression used to direct clinical decision-making for patients with advanced cancers... ESMO 2016 Congress 7-11 October, 2016 Copenhagen, Denmark Table of Contents Summary... 2 TRANSLATIONAL RESEARCH... 3 Tumour gene expression used to direct clinical decision-making for patients with advanced

More information

Managing Moderate Penetrance

Managing Moderate Penetrance Managing Moderate Penetrance Thomas Slavin, MD, FACMG Assistant Clinical Professor, Department of Medical Oncology, Division of Clinical Cancer Genetics Program Member, Cancer Control and Population Sciences

More information

The Value of Panel Testing in Inherited Breast Cancer Risk Assessment. Rodney J. Scott Division of Molecular Medicine

The Value of Panel Testing in Inherited Breast Cancer Risk Assessment. Rodney J. Scott Division of Molecular Medicine The Value of Panel Testing in Inherited Breast Cancer Risk Assessment Rodney J. Scott Division of Molecular Medicine Mutation Detection Next Generation DNA sequencing has revolutionised mutation detection

More information

UW359 Ovary 3c 3 Serous Recurrent 68 BRCA1 816delGT BRCA1 del exon 1-2. UW417 Ovary 3c 3 Serous Primary 38 BRCA1 1675delA

UW359 Ovary 3c 3 Serous Recurrent 68 BRCA1 816delGT BRCA1 del exon 1-2. UW417 Ovary 3c 3 Serous Primary 38 BRCA1 1675delA Supplementary Table 1. Cases with deleterious germline mutations, somatic HR mutations, and somatic PTEN mutations. ID Site Stage Grade Histology Tumor Age Germline mutation(s) a Somatic HR mutation(s)

More information

AVANCES EN EL TRATAMIENTO SISTEMICO DE LOS TUMORES BRCA-DEFICIENTES

AVANCES EN EL TRATAMIENTO SISTEMICO DE LOS TUMORES BRCA-DEFICIENTES AVANCES EN EL TRATAMIENTO SISTEMICO DE LOS TUMORES BRCA-DEFICIENTES Dra. Judith Balmaña Servicio de Oncología Médica Hospital Universitario Vall Hebron Barcelona jbalmana@vhio.net Preclinical evidence

More information

Triple Negative Breast Cancer

Triple Negative Breast Cancer GASCO 2016 San Antonio Breast Cancer Symposium Review Triple Negative Breast Cancer Amelia Zelnak, MD, MSc Atlanta Cancer Care Northside Hospital Cancer Institute Disclosures: consultant for Novartis,

More information

Why Test for Hereditary Cancer in Preventive Care?

Why Test for Hereditary Cancer in Preventive Care? Why Test for Hereditary Cancer in Preventive Care? Millions of people are sidelined by cancer. Wouldn't it be worth it for your patients to know their risk? background HEREDITARY (5-10%) More than 1 in

More information

Myriad Financial Assistance Program (MFAP)

Myriad Financial Assistance Program (MFAP) Myriad Financial Assistance Program (MFAP) MEDICAL CRITERIA Hereditary Cancer Products The Myriad Financial Assistance Program offers aid to patients who meet specific financial and medical requirements.

More information

PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland

PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland AWARD NUMBER: W81XWH-13-1-0484 TITLE: PRINCIPAL INVESTIGATOR: Elizabeth Swisher CONTRACTING ORGANIZATION: University of Washington REPORT DATE: 2014 TYPE OF REPORT: Annual Report PREPARED FOR: U.S. Army

More information

PARP Inhibitors: The First Synthetic Lethal Targeted Therapy

PARP Inhibitors: The First Synthetic Lethal Targeted Therapy PARP Inhibitors: The First Synthetic Lethal Targeted Therapy Christopher J. Lord 1,2* and Alan Ashworth 3* 1 The CRUK Gene Function Laboratory and 2 Breast Cancer Now Research Centre, The Institute of

More information

WHAT IS A GENE? CHROMOSOME DNA PROTEIN. A gene is made up of DNA. It carries instructions to make proteins.

WHAT IS A GENE? CHROMOSOME DNA PROTEIN. A gene is made up of DNA. It carries instructions to make proteins. WHAT IS A GENE? CHROMOSOME GENE DNA A gene is made up of DNA. It carries instructions to make proteins. The proteins have specific jobs that help your body work normally. PROTEIN 1 WHAT HAPPENS WHEN THERE

More information

Genetic Testing: who, what, why?

Genetic Testing: who, what, why? Genetic Testing: who, what, why? Gina Westhoff MD LMG Gynecologic Oncology March 16, 2019 Disclosures Speaker for Merck (unrelated to today s topic) Objectives Determine who should undergo genetic risk

More information

Edinburgh Research Explorer

Edinburgh Research Explorer Edinburgh Research Explorer Long-term responders on olaparib maintenance in high-grade serous ovarian cancer: Clinical and molecular characterization Citation for published version: Lheureux, S, Lai, Z,

More information

Treatment options in patients with early breast cancer and BRCAmutations or family history of cancer

Treatment options in patients with early breast cancer and BRCAmutations or family history of cancer PHARMACOTHERAPY 239 Treatment options in patients with early breast cancer and BRCAmutations or family history of cancer M-D. t Kint de Roodenbeke, MD 1, L. Buisserer, MD, PhD 2, M. Piccart-Gebhart, MD,

More information

Precision Genetic Testing in Cancer Treatment and Prognosis

Precision Genetic Testing in Cancer Treatment and Prognosis Precision Genetic Testing in Cancer Treatment and Prognosis Deborah Cragun, PhD, MS, CGC Genetic Counseling Graduate Program Director University of South Florida Case #1 Diana is a 47 year old cancer patient

More information

pan-canadian Oncology Drug Review Final Clinical Guidance Report Olaparib (Lynparza) for Ovarian Cancer - Resubmission September 20, 2017

pan-canadian Oncology Drug Review Final Clinical Guidance Report Olaparib (Lynparza) for Ovarian Cancer - Resubmission September 20, 2017 pan-canadian Oncology Drug Review Final Clinical Guidance Report Olaparib (Lynparza) for Ovarian Cancer - Resubmission September 20, 2017 DISCLAIMER Not a Substitute for Professional Advice This report

More information

LYNPARZA RECEIVES ADDITIONAL AND BROAD APPROVAL IN THE US FOR OVARIAN CANCER

LYNPARZA RECEIVES ADDITIONAL AND BROAD APPROVAL IN THE US FOR OVARIAN CANCER This announcement contains inside information 18 August 2017 07:00 BST LYNPARZA RECEIVES ADDITIONAL AND BROAD APPROVAL IN THE US FOR OVARIAN CANCER Lynparza's new tablet formulation approved as maintenance

More information

Current Medical Oncology Approaches to Gynecologic Cancers. Mihaela Cristea, MD Associate Professor Medical Oncology

Current Medical Oncology Approaches to Gynecologic Cancers. Mihaela Cristea, MD Associate Professor Medical Oncology Current Medical Oncology Approaches to Gynecologic Cancers Mihaela Cristea, MD Associate Professor Medical Oncology Nothing to disclose DISCLOSURE Ovarian Cancer Objectives: a. To discuss new FDA approved

More information

Abstract # 1503: Predisposing germline mutations in high grade ER+ HER2- breast cancer patients diagnosed age < 50

Abstract # 1503: Predisposing germline mutations in high grade ER+ HER2- breast cancer patients diagnosed age < 50 Abstract # 1503: Predisposing germline mutations in high grade ER+ HER2- breast cancer patients diagnosed age < 50 Garber JE 1, Tung NM 2, Elkin EP 3, Allen BA 3, Singh NA 3, Wenstrup R 3, Hartman AR 3,

More information