PARP inhibitors for breast cancer

Size: px
Start display at page:

Download "PARP inhibitors for breast cancer"

Transcription

1 PARP inhibitors for breast cancer Mark Robson, MD Memorial Sloan Kettering Cancer Center

2 Agenda Mechanism of action Clinical studies Resistance mechanisms Future directions

3 Poly (ADP-ribose) Polymerases

4 PARP Involvement in DNA Repair Helleday, Mol Oncol 211

5 PARP Inhibition in BRCA-deficient cells BRCA1 BRCA2 Farmer et al, Nature 25

6 Challenges to model PARP1 not required for base excision repair Steady state level of single strand breaks not increased with PARPi PARP1 hyperactivated in HR-defective cells PARP1 involved in non-homologous end joining PARP1 involved in restart of stalled replication forks

7 Alternative models Helleday et al Mol Oncol 211

8 Alternative models Impairs BRCA1 recruitment PARP1 involvement in POLQ-dependent pathway of NHEJ on HR-deficient cells

9 PARPi under development Compound AKA Phase Olaparib (AZ) KU59436, AZD2281 III Veliparib (AbbVie) ABT888 II/III (upcoming) Rucaparib (Clovis) PF , AG14699 I/II Niraparib (Tesaro) MK4827 III Talazoparib (Medivation) MDV38, BMN-673 III CEP-9722 (Cephalon) E716 (Eisai) I I

10 Differences among PARPi Catalytic inhibition O > V > N B, BMN673; N, niraparib; O, olaparib; R, rucaparib (promiscuous); V, veliparib PARP Trapping N=O > V B > O B > R Cytotoxicity (specific systems) N > O > V B > O B> R Murai et al Cancer Res 212, Mol Cancer Therap 214

11 Differences among PARPi Catalytic inhibition O > V > N B, BMN673; N, niraparib; O, olaparib; R, rucaparib (promiscuous); V, veliparib PARP Trapping N=O > V B > O B > R Cytotoxicity (specific systems) N > O > V B > O B> R Murai et al Cancer Res 212, Mol Cancer Therap 214

12 CLINICAL STUDIES

13 Approaches Single agent ( synthetic lethality ) Leverages defects in homologous recombination Combination with CTX or RT Does not necessarily require HR defect

14 Single agent development Best response (ITT) Olaparib 4 bid (n=27) Olaparib 1 bid (n=27) CR 1 (4%) PR 1 (37%) 6 (22%) SD 12 (44%) 12 (44%) PD 4 (15%) 9 (33%) Median PFS 5.7 mo 3.8 mo MRD days Tutt, Lancet 21

15 Study 42 : single agent olaparib basket Tumour response rates (full analysis set) Tumor type Response status, n (%) Ovarian (n=193) Breast (n=62) Pancreas (n=23) Prostate (n=8) Other (n=12) Total (n=298) Tumor response rate CR* PR* 6 (31.1) 6 (3.1) 54 (28) 8 (12.9) 8 (13) 5 (21.7) 1 (4.3) 4 (17) 4 (5.) 4 (5) 1 (8.3) 1 (8.3) 78 (26.2) 7 (2.3) 71 (23.8) SD 8 weeks SD Unconfirmed PR 78 (4) 64 (33) 12 (6) 29 (47) 22 (36) 7 (11) 8 (35) 5 (22) 3 (13) 2 (25) 2 (25) 7 (58) 6 (5) 1 (8.3) 124 (42) 99 (33) 23 (8) PD RECIST progression Early death 41 (21) 33 (17) 8 (4) 23 (37) 16 (26) 7 (11) 9 (39) 6 (26) 3 (13) 2 (25) 1 (13) 1 (13) 3 (25) 3 (25) 78 (26) 59 (2) 19 (6) Not evaluable No follow-up assessments SD <8 weeks 14 (7) 12 (6) 2 (1) 2 (3) 2 (3) 1 (4) 1 (4) 1 (8.3) 1(8.3) 18 (6) 15 (5) 3 (1) Kaufman et al. J Clin Oncol 215;33:244-5

16 Olaparib + Cisplatin Phase 1 Could not find tolerable olaparib dose with 75/m2 cisplatin Olaparib 5 bid D1-5 + cisplatin 6/m2 tolerable Good OR (71% (12/17)) in BRCA-BC, including 2 durable responses > 2 yrs in patients on olaparib monotherapy after combination Balmaña et al, Ann Oncol 214 Olaparib-Topetecan also very toxic (Samol, Invest new Drug 212)

17 Other combinations *ispy success in neoadjuvant therapy of unselected TNBC*

18 PARPi + PIK3CAi in BRCA1-BC Jukevar et al, Cancer Discovery 212;2:148

19 Challenges to getting approval Single agent vs combination What combination? What endpoint? Cross-over (official/ unofficial) Companion diagnostic

20 Olaparib in platinum-sensitive ovarian (Maintenance after carboplatin/paclitaxel induction) Probability of progression-free survival No. at risk Olaparib Placebo Months since randomization Olaparib Placebo Hazard ratio,.35 (95% CI, ) P<.1 No. of patients/ Total no (%) 6/136 (44.1) 93/129 (72.1) Median Progression-free Survival (mo) PFS Analysis in gbrca (ODAC) HR.17 (95% CI.9-.32) PFS 11.2 v 4.1 mo No difference in OS (32.9 v 3.2 mo) Ledermann J et al. N Engl J Med 212;366:

21 Study 42 : single agent olaparib basket Tumour response rates (full analysis set) Tumor type Response status, n (%) Ovarian (n=193) Breast (n=62) Pancreas (n=23) Prostate (n=8) Other (n=12) Total (n=298) Tumor response rate CR* PR* 6 (31.1) 6 (3.1) 54 (28) 8 (12.9) 8 (13) 5 (21.7) 1 (4.3) 4 (17) 4 (5.) 4 (5) 1 (8.3) 1 (8.3) 78 (26.2) 7 (2.3) 71 (23.8) SD 8 weeks SD Unconfirmed PR 78 (4) 64 (33) 12 (6) 29 (47) 22 (36) 7 (11) 8 (35) 5 (22) 3 (13) 2 (25) 2 (25) 7 (58) 6 (5) 1 (8.3) 124 (42) 99 (33) 23 (8) PD RECIST progression Early death 41 (21) 33 (17) 8 (4) 23 (37) 16 (26) 7 (11) 9 (39) 6 (26) 3 (13) 2 (25) 1 (13) 1 (13) 3 (25) 3 (25) 78 (26) 59 (2) 19 (6) Not evaluable No follow-up assessments SD <8 weeks 14 (7) 12 (6) 2 (1) 2 (3) 2 (3) 1 (4) 1 (4) 1 (8.3) 1(8.3) 18 (6) 15 (5) 3 (1) Kaufman et al. J Clin Oncol 215;33:244-5

22 Phase III OLympiAD (OLaparib in Advanced Disease) Metastatic gbrca-bc Prior anthra/taxane -2 prior for mbc No prior platinum Physician s choice (capecitabine, vinorelbine, eribulin) Olaparib Primary endpoint: PFS (no cross-over) Secondary: OS, PFS2 Planned sample size: 31 patients Nearly identical studies planned with niraparib (BIG/EORTC) and BMN-673 (Industry-sponsored)

23 Expanding the use of PARPi Triple negative breast cancer 8% of BRCA1-BC are TNBC Most BRCA1-BC are basal-like Some sporadic TNBC have BRCA1 expression by IHC Sporadic TNBC have genomic instability similar to BRCA1-BC

24 Expanding beyond gbrca Olaparib 4 mg po BID 1 gbrca-bc and 16 non-brca TNBC Gelmon et al, Lancet Oncol 211

25 ATM Deficient Cancer Yung-Jue Bang et al. JCO 215;33:

26 Genomic Aberrations in DNA Repair in Patients with Metastatic, Castration-Resistant Prostate Cancer Mateo J et al. New Engl J Med 215;373:1697

27 RESISTANCE TO PARP INHIBITORS

28 Mechanisms of resistance Panagiotis A. Konstantinopoulos et al. Cancer Discov 215;5:

29 Platinum Cross-Resistance? Patients with gbrca1/2m ovarian cancer and measurable disease at baseline who had received 3 prior chemotherapy regimens (n = 137). Platinum Status Confirmed Responders ORR, % (95% CI) Median DoR, months (95% CI) Total (n=137) (26-42) 7.9 ( ) Plt Sensitive (n=39) Plt resistant (n=81) Plt refractory (n=14) (3-63) 8.2 ( ) 24 3 (2-41) 8. ( ) 2 14 (2-43) 6..4 ( ) Unknown (n=3) 2 67 (9-99) 6.3 ( ) Domchek et al, Gyn Oncology 216

30 Summary PARP inhibition is a novel therapeutic approach to BRCAm breast cancer Promising activity in early trials, but obtaining regulatory approval has been challenging Effectiveness outside of gbrcam setting a topic of active exploration Biomarkers of response beyond gbrcam sorely needed

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

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

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

Expert Review: The Role of PARP Inhibition in the Treatment of Breast Cancer. Reference Slides

Expert Review: The Role of PARP Inhibition in the Treatment of Breast Cancer. Reference Slides Expert Review: The Role of PARP Inhibition in the Treatment of Breast Cancer Reference Slides Overview BRCA Mutations and Breast Cancer Patients with BRCA mutations have an estimated 55% to 65% cumulative

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 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

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

Medicina de precisión en cáncer de ovario: Determinación de BRCA germinal y somático 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 Introduction Ovarian cancer is the fifth

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

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

Carrier Frequency. Breast Cancer and Treatment Options in Patients with BRCA1/2 mutations. Olivia Pagani On behalf of Bella Kaufman

Carrier Frequency. Breast Cancer and Treatment Options in Patients with BRCA1/2 mutations. Olivia Pagani On behalf of Bella Kaufman Breast Cancer and Treatment Options in Patients with BRCA1/2 mutations Olivia Pagani On behalf of Bella Kaufman Carrier Frequency Prevalence of an altered disease gene in a given population 1 Background

More information

Breast Cancer and Treatment Options in Patients with BRCA1/2 mutations. Olivia Pagani On behalf of Bella Kaufman

Breast Cancer and Treatment Options in Patients with BRCA1/2 mutations. Olivia Pagani On behalf of Bella Kaufman Breast Cancer and Treatment Options in Patients with BRCA1/2 mutations Olivia Pagani On behalf of Bella Kaufman Carrier Frequency Prevalence of an altered disease gene in a given population Background

More information

Dieta Brandsma, Department of Neuro-oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands

Dieta Brandsma, Department of Neuro-oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands What is hot in breast cancer brain metastases? Dieta Brandsma, Department of Neuro-oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands 8th Annual Brain Metastases Research and Emerging Therapy

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

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

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

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

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

Management of Triple Negative Breast Cancer. Giuseppe Curigliano MD, PhD University of Milano and European Institute of Oncology

Management of Triple Negative Breast Cancer. Giuseppe Curigliano MD, PhD University of Milano and European Institute of Oncology Management of Triple Negative Breast Cancer Giuseppe Curigliano MD, PhD University of Milano and European Institute of Oncology Outline Heterogeneity of TNBC Targeting TNBC by subtypes New antibody drug

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

Targeting DNA repair in BRCA 1/2 and Triple Negative Breast Cancer

Targeting DNA repair in BRCA 1/2 and Triple Negative Breast Cancer Targeting DNA repair in BRCA 1/2 and Triple Negative Breast Cancer Andrew Tutt, MB ChB, PhD Consultant Oncologist/Director Breakthrough Breast Cancer Research Unit King s Health Partners Academic Health

More information

Post-ASCO 2017 Cancer du sein Triple Négatif

Post-ASCO 2017 Cancer du sein Triple Négatif Post-ASCO 217 Cancer du sein Triple Négatif A.Ladjeroud, K.Bouzid Centre Pierre et Marie Curie- Alger Oran, 3 Septembre 217 Phase III Investigation of Neoadjuvant Carboplatin ± Veliparib in Combination

More information

PARP Inhibitors and DNA Damage Repair

PARP Inhibitors and DNA Damage Repair Breakthrough in Triple Negative Breast Cancer PARP Inhibitors and DNA Damage Repair Seock-Ah Im M.D. PhD. Department of Internal Medicine Seoul National University Hospital Contents Introduction Hallmark

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

6/13/17. Disclosures. Treating Breast Cancer in People with Mutations. Off Label Use. I will be discussing off label use of medications today.

6/13/17. Disclosures. Treating Breast Cancer in People with Mutations. Off Label Use. I will be discussing off label use of medications today. Treating Breast Cancer in People with Mutations Steven J. Isakoff, MD, PhD Massachusetts General Hospital Cancer Center June 9, 2017 sisakoff@partners.org Disclosures Company ² Myriad Genetics ² AbbVie

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

Supplementary Appendix

Supplementary Appendix Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(adp-ribose)

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

Triple Negative Breast Cancer. Eric P. Winer, MD Dana-Farber Cancer Institute Harvard Medical School Boston, MA October, 2008

Triple Negative Breast Cancer. Eric P. Winer, MD Dana-Farber Cancer Institute Harvard Medical School Boston, MA October, 2008 Triple Negative Breast Cancer Eric P. Winer, MD Dana-Farber Cancer Institute Harvard Medical School Boston, MA October, 2008 Triple Negative Breast Cancer 15% 25% Triple Negative 20% HER2+ ER+ Low Grade

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

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

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

Systemic therapy of triple negative advanced breast cancer. Giuseppe Curigliano MD, PhD Breast Cancer Program Division of Early Drug Development

Systemic therapy of triple negative advanced breast cancer. Giuseppe Curigliano MD, PhD Breast Cancer Program Division of Early Drug Development Systemic therapy of triple negative advanced breast cancer Giuseppe Curigliano MD, PhD Breast Cancer Program Division of Early Drug Development Outline State of the Art in the management of TN advanced

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

Clinical Research on PARP Inhibitors and Triple-Negative Breast Cancer (TNBC)

Clinical Research on PARP Inhibitors and Triple-Negative Breast Cancer (TNBC) Clinical Research on PARP Inhibitors and Triple-Negative Breast Cancer (TNBC) Eric P Winer, MD Disclosures for Eric P Winer, MD No real or apparent conflicts of interest to disclose Key Topics: PARP and

More information

Triple Negative Breast Cancer: Part 2 A Medical Update

Triple Negative Breast Cancer: Part 2 A Medical Update Triple Negative Breast Cancer: Part 2 A Medical Update April 29, 2015 Tiffany A. Traina, MD Breast Medicine Service Memorial Sloan Kettering Cancer Center Weill Cornell Medical College Overview What is

More 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

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

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

La malattia triplo negativa metastatica: quali trattamenti nella pratica clinica?

La malattia triplo negativa metastatica: quali trattamenti nella pratica clinica? 2018 CARCINOMA MAMMARIO: I TRAGUARDI RAGGIUNTI E LE NUOVE SFIDE La malattia triplo negativa metastatica: quali trattamenti nella pratica clinica? Roma, 27 Ottobre 2018 Relatore: Francesca Poggio Disclosure

More information

Amir Sonnenblick, Evandro de Azambuja, Hatem A. Azim Jr and Martine Piccart

Amir Sonnenblick, Evandro de Azambuja, Hatem A. Azim Jr and Martine Piccart An update on inhibitors moving to the adjuvant setting Amir Sonnenblick, Evandro de Azambuja, Hatem A. Azim Jr and Martine Piccart REVIEWS Abstract Inhibition of poly(adp-ribose) polymerase () enzymes

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

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

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

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

Demystifying Clinical Trials and some exciting new directions

Demystifying Clinical Trials and some exciting new directions Demystifying Clinical Trials and some exciting new directions Elise C. Kohn, MD Head, Gynecologic Cancer Therapeutics, Clinical Investigations Branch Cancer Therapy Evaluation Program National Cancer Institute

More information

Edith A. Perez, Ahmad Awada, Joyce O Shaughnessy, Hope Rugo, Chris Twelves, Seock-Ah Im, Carol Zhao, Ute Hoch, Alison L. Hannah, Javier Cortes

Edith A. Perez, Ahmad Awada, Joyce O Shaughnessy, Hope Rugo, Chris Twelves, Seock-Ah Im, Carol Zhao, Ute Hoch, Alison L. Hannah, Javier Cortes BEACON: A Phase 3 Open-label, Randomized, Multicenter Study of Etirinotecan Pegol (EP) versus Treatment of Physician s Choice (TPC) in Patients With Locally Recurrent or Metastatic Breast Cancer Previously

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

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

Lonnie Moulder, CEO Leerink Global Healthcare Conference February 12, 2015

Lonnie Moulder, CEO Leerink Global Healthcare Conference February 12, 2015 Lonnie Moulder, CEO Leerink Global Healthcare Conference February 12, 2015 Safe Harbor Statement Statements made in this presentation about TESARO, Inc. that are not descriptions of historical facts are

More information

Cancers du Sein Métastatiques

Cancers du Sein Métastatiques Cancers du Sein Métastatiques Véronique Diéras Journée Laurence Leroyer Rennes 18 mai 2018 Plan ESME Inhibiteurs CDK 4/6 RH+ Inhibiteurs PARP Anticorps drogue-conjugués Perspectives 2018-2019 ESME Time

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

Lynparza. Lynparza (olaparib) Description

Lynparza. Lynparza (olaparib) Description Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.21.52 Subject: Lynparza Page: 1 of 5 Last Review Date: March 16, 2018 Lynparza Description Lynparza (olaparib)

More information

Objectives: Describe poly-adp-ribose polymerase (PARP) inhibitors mechanism of action.

Objectives: Describe poly-adp-ribose polymerase (PARP) inhibitors mechanism of action. 1 2 3 Role of PARP Inhibitors in Metastatic Breast Cancer Catie Chatowsky, PharmD PGY1 Pharmacy Resident Disclosure: I have nothing to disclose. Objectives: Describe poly-adp-ribose polymerase (PARP) inhibitors

More information

New Developments in Ovarian Cancer

New Developments in Ovarian Cancer New Developments in Ovarian Cancer Daniela Matei, MD Professor Gynecology Oncology Northwestern University Feinberg School of Medicine Robert H Lurie Comprehensive Cancer Center Outline Recent and ongoing

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

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

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

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

Treatment of Triple Negative Breast Cancer. Giuseppe Curigliano MD, PhD University of Milano and European Institute of Oncology

Treatment of Triple Negative Breast Cancer. Giuseppe Curigliano MD, PhD University of Milano and European Institute of Oncology Treatment of Triple Negative Breast Cancer Giuseppe Curigliano MD, PhD University of Milano and European Institute of Oncology Outline Neoadjuvant treatment in triple negative EBC Picking optimal adjuvant

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

How I Approach Triple Negative Breast Cancer (TNBC) Dr Tan Yew Oo Specialist Medical Oncologist Farrer Park Medical Centre Singapore

How I Approach Triple Negative Breast Cancer (TNBC) Dr Tan Yew Oo Specialist Medical Oncologist Farrer Park Medical Centre Singapore How I Approach Triple Negative Breast Cancer (TNBC) Dr Tan Yew Oo Specialist Medical Oncologist Farrer Park Medical Centre Singapore Connexion: Integrated Healthcare & Hospitality Complex Levels 11 to

More information

Treatment of Recurrent Ovarian Cancer

Treatment of Recurrent Ovarian Cancer Treatment of Recurrent Ovarian Cancer Mihaela Cristea, MD Associate Professor Medical Oncology, City of Hope November 11, 2016 No disclosures Financial Disclosure Epithelial Ovarian Cancer Subtypes and

More information

Highlights of. Metastatic & Advanced Breast Cancer

Highlights of. Metastatic & Advanced Breast Cancer Highlights of Metastatic & Advanced Breast Cancer 1 Financial Disclosure(s) I currently have or have had the following relevant financial relations to disclose: Speaker s Bureau: Novartis 2 Off Label Use

More information

Patient-Centric Science-Based Performance-Driven

Patient-Centric Science-Based Performance-Driven Patient-Centric Science-Based Performance-Driven Cowen & Co. 38 th Annual Health Care Conference Michael Pehl, President and Chief Executive Officer March 12, 2018 Forward-Looking Statements This presentation,

More information

Utilizing Clinical Pathways for Remission Maintenance in Ovarian Cancer

Utilizing Clinical Pathways for Remission Maintenance in Ovarian Cancer Utilizing Clinical Pathways for Remission Maintenance in Ovarian Cancer This educational activity is supported by educational grants from AbbVie, and TESARO, Inc. Faculty Robert P. Edwards MD Professor

More information

New Avenues for the development and evaluation of therapy: Complex, multi-pronged, not one size fitting all

New Avenues for the development and evaluation of therapy: Complex, multi-pronged, not one size fitting all New Avenues for the development and evaluation of therapy: Complex, multi-pronged, not one size fitting all Antoine Yver MD MSC Senior VP & Head Oncology Global Medicines Development AstraZeneca, Gaithersburg

More information

"BRCAness," PARP and the Triple-Negative Phenotype

BRCAness, PARP and the Triple-Negative Phenotype "BRCAness," PARP and the Triple-Negative Phenotype Prof Alan Ashworth, FRS Disclosures for Professor Alan Ashworth, FRS Consulting Agreements GlaxoSmithKline, Pfizer Inc Patent AstraZeneca Pharmaceuticals

More information

Update on Breast Cancer

Update on Breast Cancer Update on Breast Cancer William J. Gradishar, MD Professor of Medicine Robert H. Lurie Comprehensive Cancer Center Feinberg School of Medicine Northwestern University Overview PARP Inhibitors Neoadjuvant

More information

Developmental Therapeutics for HCC, Colorectal Cancer, and Pancreatic Cancer. Manish Sharma, MD Developmental Therapeutics Symposium April 20, 2018

Developmental Therapeutics for HCC, Colorectal Cancer, and Pancreatic Cancer. Manish Sharma, MD Developmental Therapeutics Symposium April 20, 2018 Developmental Therapeutics for HCC, Colorectal Cancer, and Pancreatic Cancer Manish Sharma, MD Developmental Therapeutics Symposium April 20, 2018 Disclosure Information 23 rd Annual Developmental Therapeutics

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

Triple Negative Breast cancer New treatment options arenowhere?

Triple 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 information

ENFERMEDAD AVANZADA Qué hacemos con el triple negativo? Nuevas aproximaciones

ENFERMEDAD AVANZADA Qué hacemos con el triple negativo? Nuevas aproximaciones ENFERMEDAD AVANZADA Qué hacemos con el triple negativo? Nuevas aproximaciones Javier Cortes, Hospital Universitario Ramon y Cajal, Madrid Vall d Hebron Institute of Oncology (VHIO), Barcelona Triple Negative

More information

Ovarian Cancer: Implications for the Pharmacist

Ovarian Cancer: Implications for the Pharmacist Ovarian Cancer: Implications for the Pharmacist Megan May, Pharm.D., BCOP Objectives Describe the etiology and pathophysiology of ovarian cancer Outline the efficacy and safety of treatment options for

More information

For more than 20 years, researchers

For more than 20 years, researchers June 2018 FTase Inhibition Holds Promise for RAS Targeting and Beyond By William Pass, DVM For more than 20 years, researchers have known that the RAS pathway is involved in a wide variety of cancer types.

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

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

Maintenance paradigm in non-squamous NSCLC

Maintenance paradigm in non-squamous NSCLC Maintenance paradigm in non-squamous NSCLC L. Paz-Ares Hospital Universitario Virgen del Rocío Sevilla Agenda Theoretical basis The data The comparisons Agenda Theoretical basis The data The comparisons

More information

Hereditary Gynecologic Cancer 15 Years of Progress

Hereditary Gynecologic Cancer 15 Years of Progress Hereditary Gynecologic Cancer 15 Years of Progress Bethan Powell, M. D. Kaiser Permanente UCSF Gynecologic Cancer Risk Program Hereditary Gynecologic Cancer Syndromes BRCA 1 and 2: ovarian Lynch: ovarian/endometrial

More information

Terapia sistemica neoadiuvante: in quali tumori? Quali risultati? Dott. Giacomo Pelizzari

Terapia 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 information

Pfizer Presents Final Phase 2 Data on Investigational PARP Inhibitor Talazoparib in Patients with Germline BRCA-Positive Advanced Breast Cancer

Pfizer Presents Final Phase 2 Data on Investigational PARP Inhibitor Talazoparib in Patients with Germline BRCA-Positive Advanced Breast Cancer For immediate release June 3, 2017 Media Contact: Sally Beatty (212) 733-6566 Investor Contact: Ryan Crowe (212) 733-8160 Pfizer Presents Final Phase 2 Data on Investigational PARP Inhibitor Talazoparib

More information

Oncofocus. Patient Test Report

Oncofocus. Patient Test Report Oncofocus Patient Test Report Lead Clinical Scientist: Keeda Snelson Senior BMS: Tiffany Haddow Date: 04 May 2017 1 of 13 Surname Forename DOB Gender Histology # Primary site Tumour subtype Tissue Type

More information

HDAC Inhibitors and PARP inhibitors. Suresh Ramalingam, MD Associate Professor Chief of Thoracic Oncology Emory University School of Medicine

HDAC Inhibitors and PARP inhibitors. Suresh Ramalingam, MD Associate Professor Chief of Thoracic Oncology Emory University School of Medicine HDAC Inhibitors and PARP inhibitors Suresh Ramalingam, MD Associate Professor Chief of Thoracic Oncology Emory University School of Medicine Histone Acetylation HAT Ac Ac Ac Ac HDAC Ac Ac Ac Ac mrna DACs

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

Convegno Nazionale AIOM Giovani 2016: News in Oncology. Daniele Alesini. Istituto Nazionale dei Tumori Regina Elena

Convegno Nazionale AIOM Giovani 2016: News in Oncology. Daniele Alesini. Istituto Nazionale dei Tumori Regina Elena Convegno Nazionale AIOM Giovani 2016: News in Oncology Daniele Alesini Istituto Nazionale dei Tumori Regina Elena Something Old Something New Something Borrowed Something Blue DOCETAXEL: BACK AND FORTH

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

Novel treatment strategies in triple-negative breast cancer: specific role of poly(adenosine diphosphate-ribose) polymerase inhibition

Novel treatment strategies in triple-negative breast cancer: specific role of poly(adenosine diphosphate-ribose) polymerase inhibition Pharmacogenomics and Personalized Medicine open access to scientific and medical research Open Access Full Text Article Novel treatment strategies in triple-negative breast cancer: specific role of poly(adenosine

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

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

TNBC: 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 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 information

Challenges In The Development Of Novel Therapeutics In Ovarian Cancer Tony Ho, MD Global Medicine Leader Medi4736, Vice President, AstraZeneca

Challenges In The Development Of Novel Therapeutics In Ovarian Cancer Tony Ho, MD Global Medicine Leader Medi4736, Vice President, AstraZeneca Challenges In The Development Of Novel Therapeutics In Ovarian Cancer Tony Ho, MD Global Medicine Leader Medi4736, Vice President, AstraZeneca The views and opinions expressed herein are my own and do

More information

Understanding Biological Activity to Inform Drug Development

Understanding Biological Activity to Inform Drug Development National Cancer Policy Forum Understanding Biological Activity to Inform Drug Development December 12, 2016 Wolfgang Weber Molecular Imaging and Therapy Service Department of Radiology RECIST Response

More information

Genetics of Breast and Ovarian Cancer: Risk Assessment, Screening, and Risk Reduction

Genetics of Breast and Ovarian Cancer: Risk Assessment, Screening, and Risk Reduction Genetics of Breast and Ovarian Cancer: Risk Assessment, Screening, and Risk Reduction Forum INCA-ASCO sobre Cancer Hereditario e Predisposicao Genetica ao Cancer Jeffrey N. Weitzel, M.D. Professor of Oncology

More information

CONSIDERATIONS IN DEVELOPMENT OF PEMBROLIZUMAB IN MSI-H CANCERS

CONSIDERATIONS IN DEVELOPMENT OF PEMBROLIZUMAB IN MSI-H CANCERS CONSIDERATIONS IN DEVELOPMENT OF PEMBROLIZUMAB IN MSI-H CANCERS December 2017 Christine K. Gause, Ph.D Executive Director, Biostatistics. 2 Microsatellite Instability-High Cancer - USPI KEYTRUDA is indicated

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

Emerging Therapies for Triple Negative Breast Cancer

Emerging Therapies for Triple Negative Breast Cancer Emerging Therapies for Triple Negative Breast Cancer Joseph A. Sparano, MD Professor of Medicine & Women s Health Albert Einstein College of Medicine Associate Chairman, Department of Oncology Montefiore

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

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

Eribulin for locally advanced or metastatic breast cancer third line; monotherapy

Eribulin for locally advanced or metastatic breast cancer third line; monotherapy Eribulin for locally advanced or metastatic breast cancer third line; monotherapy April 2009 This technology summary is based on information available at the time of research and a limited literature search.

More information

INMUNOTERAPIA I. Dra. Virginia Calvo

INMUNOTERAPIA I. Dra. Virginia Calvo INMUNOTERAPIA I Dra. Virginia Calvo LBA62. Health-related quality of life (HRQoL) for Pembrolizumab or placebo plus Carboplatin and Paclitaxel or nab-paclitaxel in patients with metastatic squamous NSCLC:

More information

Feasibility of Clinical Trial Implementation Genetically Eligible Prostate Cancer Patients Oliver Sartor, MD Cathryn E, Garvey, MS December 3, 2015

Feasibility of Clinical Trial Implementation Genetically Eligible Prostate Cancer Patients Oliver Sartor, MD Cathryn E, Garvey, MS December 3, 2015 Feasibility of Clinical Trial Implementation Genetically Eligible Prostate Cancer Patients Oliver Sartor, MD Cathryn E, Garvey, MS December 3, 2015 Study Name Feasibility of Patient Population for proposed

More information