EVOLUTION OF PARP INHIBITORS IN OVARIAN CANCER

Slides:

Advertisements

Similar presentations

Efficacy of BSI-201, a PARP-Inhibitor in combination with Gemcitabine/Carboplatin in Triple Negative Breast Cancer: Randomized.

Advertisements

Progress Against Ovarian Cancer. 1970–1979 Progress Against Ovarian Cancer 1970– : First effective combination chemotherapy regimen for ovarian.

Gynecologic Oncology Group Gynecologic Oncology Group Uterine Corpus Trials: GCIG David Scott Miller, M.D., F.A.C.O.G., F.A.C.S. Director and Dallas Foundation.

O VARIAN C ANCER C LINICAL T RIALS P LANNING M EETING Unanswered Questions in Upfront Therapy IP Therapy Issue Keiichi Fujiwara, MD, PhD Saitama Medical.

A trial for women with –‘Triple negative’ breast cancer (TNBC) –Localised to breast +/- lymph nodes –Recommended standard treatment involves NEPTUNE Taxane.

‍‍‍‍Chemotherapy in epithelial ovarian cancer. Dr.Azarm.

Can We Define Tumors That Will Respond to PARP Inhibitors? A Phase II Correlative Study of Olaparib in Advanced Serous Ovarian Cancer and Triple-Negative.

CELLULAR BIOLOGY IN BREAST CANCER JESSE ELLMAN MD SEPT 2010 CLINICAL ASSISTANT PROFESSOR DEPT OB GYN AND WOMENS HEALTH WE MAY BE ENTERING A NEW PHASE.

Cancer Estimated US Cancer Cases Cancer Incidence Rates for Women, USA.

BRCA2 Clark Cunningham March 26, 2015 BIOL445 American Cancer Society, eastcancer/make-a-pink-ribbon-lapel-pin,

10 Minutes Talk 吳華席 Hua-Hsi Wu, MD OB/GYN, VGH-TPE Sep 08, 2008.

WHAT WILL THE KEY ISSUES IN END- POINT ASSESSMENT BE, IN FUTURE OVARIAN CANCER TRIALS INVOLVING NOVEL TARGETED AGENTS? first line treatment maintenance/consolidation.

Audeh MW et al. ASCO 2009; Abstract (Clinical Science Symposium)

ENDOMETRIAL CARCINOMA UPDATES Dr Marco Matos Gold Coast Cancer Care, Gold Coast University Hospital and Pacific Private Oncology Group.

Genomic Medicine Rebecca Tay Oncology Registrar. What is Genomic Medicine? personalised, precision or stratified medicine.

Department of Surgical, Oncological and Oral Sciences U.O.C Medical Oncology Director: Prof A. Russo Ovarian cancer Case Report 1 Dr. Lorena Incorvaia,

RANDOMIZED PHASE II STUDY OF NABPACLITAXEL, IN RECURRENT ADVANCED OR METASTATIC CERVICAL CANCER MITO CER-NAB Enrica Mazzoni, MD Medical Oncology & Breast.

Clinical and Research Updates in Gynecologic Oncology

Case Discussion: Second Opinion

Challenges for the treatment of breast cancer

Volume 12, Issue 9, Pages (September 2011)

Ovarian cancer update Kentucky cancer Registry 9/8/2016

CCO Independent Conference Coverage

Homologous recombination deficiency (HRD) of high grade serous ovarian tumors from the NOVA Phase III clinical study Keith Wilcoxen,1 Christopher Neff,2.

SOLO2: Safety, HRQoL With Maintenance Olaparib in Germline BRCA-Mutated Platinum-Sensitive Relapsed Serous Ovarian Cancer CCO Independent Conference Highlights*

State of the Art in BRCA-Mutated Ovarian Cancer

Patient Case 1 Patient Case 1: PET/CT Scan.

Rangel College of Pharmacy

An Introduction to DNA Damage Repair in Cancer: Beyond PARP

PARP Inhibition: The New Frontier in Recurrent Ovarian Cancer

BRCA, HRR Deficiency, and PARP Inhibitors

The Nurse View.

MOCA Living Well: Understanding PARP Inhibitors in Ovarian Cancer

The Nurse View: Best Practices in Advanced Non-Small Cell Lung Cancer

PARP and Other DNA Damage Repair Inhibitors in Solid Tumors: An Update

Activity Goals. Perspectives on PARP Inhibitors in Ovarian Cancer Has the Time Come for Individualized Care?

PARP Inhibitors and Cancer: What Do You Need to Know?

GEMSTONE Educational Case Summary

Managing gBRCA-Positive Metastatic Breast Cancer

Optimizing Combination Endocrine Therapy in HR-Positive Advanced Breast Cancer.

Individualizing Care in Ovarian Cancer

GEMSTONE Educational Case Summary

What is the role of genetic testing in patients with ovarian cancer?

This program will include a discussion of off-label treatment and investigational agents not approved by the FDA for use in the United States, and data.

PARP Inhibitors and Ovarian Cancer: What Did Data From Washington, DC, Tell Us?

Patient Selection for PARP Inhibitors:

Maintenance Therapy in Advanced Ovarian Cancer

Chairs Sven Mahner (Germany) Antonio González-Martín (Spain)

PARP Inhibitors.

GEMSTONE Educational Case Summary

Molecular Testing in Ovarian Cancer: Is the Time Now?

Conclusion Dr Antonio González Martín Head of Medical Oncology

Parp Inibitori nel carcinoma ovarico in pazienti con o senza mutazione di BRCA Giorgio Valabrega FPO IRCCS Candiolo Università degli studi di Torino.

PARP Inhibitors in Cancer Therapy: Promise, Progress, and Puzzles

Practical Guidance on the Management of Pan-Negative NSCLC

MAINTENANCE THERAPY WITH PARP INHIBITORS

Dr Axel Walther Head of Research Bristol Cancer Institute UK

Clinical Trials Oct. 6, Lyon France

Translating Germline Cancer Risk into Precision Prevention

PARP Inhibitors in Cancer Therapy: Promise, Progress, and Puzzles

The latest clinical evidence on PARP inhibitor maintenance therapy

Volume 147, Issue 3, Pages (December 2017)

What Does BRCA Have to Do With It? PARP Inhibitors in Ovarian Cancer

Objective response rate in patients with BRCA-mutated HER2-negative breast cancer treated with PARPi versus those treated with monochemotherapy (controls).

Efficacy of BSI-201, a PARP Inhibitor, in Combination with Gemcitabine/Carboplatin (GC) in Triple Negative Metastatic Breast Cancer (mTNBC): Results.

Clinical Focus.

Volume 163, Issue 2, (October 2015)

(A) Progression-free survival in patients with BRCA-mutated HER2-negative breast cancer treated with PARPi versus those treated with monochemotherapy (controls).

Optimizing Patient Outcomes in Metastatic Triple-Negative Breast Cancer.

Presentation transcript:

EVOLUTION OF PARP INHIBITORS IN OVARIAN CANCER Prof Dr Sven Mahner, MD Chair and Director Department of Obstetrics & Gynaecology University Hospital Munich, Ludwig-Maximilians-University, Munich, Germany ESMO 2018 Munich, Germany

Ovarian carcinoma is a cancer with lethal outcome 5–11 /100,000 Incidence rate1 7th most common cancer in women worldwide1 4th most common gynaecological cancer after breast, cervical & uterine carcinoma2 8th most lethal cancer in women1 WCRF: Worldwide data. https://www.wcrf.org/dietandcancer/ovarian-cancer . Accessed 5 October 2018. World Health Organization. Cancer Today. http://gco.iarc.fr/today/online-analysis-table?v=2018&mode=cancer&mode_population=continents&population=900&populations=900&key=asr&sex=2&cancer=39&type=0&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&nb_items=5&group_Accessed 5 October 2018.

Advances in chemotherapy before maintenance in ovarian cancer Five-year survival 15% 30% First use of carboplatin First use of cisplatin First use of paclitaxel Key advances in chemotherapy 1970 1980 1990

Next line of chemotherapy Standard chemotherapy strategy ‘Optimisation of treatment-free interval’ Debulking surgery Next line of chemotherapy Chemotherapy Watch & Wait Tumour volume treatment-free interval Recurrence Symptoms Time

traditional Watch & Wait PARPi Maintenance therapy A paradigm shift with the introduction of PARP inhibitor maintenance therapy Debulking surgery Chemotherapy traditional Watch & Wait PARPi Maintenance therapy Tumour volume Treatment-free interval Recurrence Symptoms Point of decision Maintenance Maintenance goals: Optimise benefit of chemotherapy Increase disease control and symptoms Improve survival (PFS & OS) Minimise toxicity and negative effects on QoL Time

Development of PARP inhibitors 1960 1980 2000 2010 2012 2013 2014 2016 2017 2018 1963 Detection of poly (ADP-ribose) in nuclei 1977 Purification of PARP-1 1980 Discovery of benzamide as a competitive PARP inhibitor Role for nuclear PARPs in DNA damage repair 1987 Cloning of PARP-1 gene 1994/1995 Cloning of BRCA1 & BRCA2 genes 2005 BRCA1/2-deficient cells are sensitive to PARPi 2012 Study 19 Phase II olaparib 2013 Start NOVA study 2014 Approval olaparib in gBRCA 2017 Approval niraparib for gBRCA and non- gBRCA in US & EU ARIEL 3 rucaparib SOLO2 olaparib 2016 NOVA results at ESMO 2018 Approval olaparib tablets* in US & EU Approval rucaparib* in US * independent of BRCA mutation status Adapted from Lin kY, Kraus WL. Cell 2017;169(2):183. doi: 10.1016/j.cell.2017.03.034.