1. 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

2. 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. . Accessed 5 October 2018.
World Health Organization. Cancer Today. 5 October 2018.

3. 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

4. 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

5. 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

6. 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: /j.cell