What s New in Ovarian Cancer Research? Novel Therapeutics for Ovarian Cancer
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1 What s New in Ovarian Cancer Research? Novel Therapeutics for Ovarian Cancer Scott Kaufmann, M.D., Ph.D. Mayo Clinic Division of Oncology Research October 27, 2012
2 Where we are now. Surgery Front-line chemotherapy Carboplatin + taxane
3 Where we want to be.
4 Approaches to improving therapy for ovarian cancer Apply new drugs that exploit the unique genetic susceptibilities of ovarian cancer Improving the effectiveness of existing drugs Develop new, non-chemotherapy approaches
5 Approaches to improving therapy for ovarian cancer Apply new drugs that exploit the unique genetic susceptibilities of ovarian cancer An update on PARP inhibitors
6 What is PARP? PARP inhibitors The poly(adp-ribose) polymer then helps regulate the response to the DNA damage that activated PARP.
7 Taking a new approach based on genomics. Why are PARP inhibitors thought to be effective in ovarian cancer? PARP PARP Strategies: Combine PARPi with chemotherapy Single-agent PARPi Test potential predictors of sensitivity
8 Current status of PARP inhibitors Olaparib (AstraZeneca) Administered orally twice a day Side effects: low platelets, sleepiness Published trials: 30-40% response in relapsed ovarian cancers with BRCA1/2 mutations. Prolongs time to recurrence when given after chemotherapy completed for relapsed ovarian cancer Veliparib (Abbott) Administered orally twice a day Multiple ongoing trials sponsored by NCI Promising single-agent activity in relapsed ovarian cancer with BRCA1/2 mutations. Will be included in GOG phase III trial Rucaparib (Clovis) Administered orally twice a day (new trial ongoing) Side effects: low white blood cells (neutrophils)
9 What to expect from PARP inhibitors Can be administered orally Not as many side effects as conventional chemotherapy Work in much the same way as chemotherapy might be more effective early in treatment Will often be combined with chemotherapy
10 In vitro/in vivo pharmacology Target definition and mechanism How do new therapies arise? SPORES, RO1s, MOCA or Pharma Preclinical pharmacology PK and metabolism Phase I testing Safety and response Preliminary effectiveness analysis Mayo Phase II consortium ACTION Phase II testing Comparative testing GOG Phase III testing
11 PARP inhibitor trials at Mayo Open Topotecan + Veliparib (ABT-888) Soon-to-open Floxuridine + Veliparib Opening with a longer timeframe GOG: Carboplatin + Taxol ± Veliparib
12 Approaches to improving therapy for ovarian cancer Apply new drugs that exploit the unique genetic susceptibilities of ovarian cancer Improving the effectiveness of existing drugs Develop new, non-chemotherapy approaches
13 Making existing drugs better by exploiting genomics. Upcoming trial: gemcitabine + MK-8776 (Chk1 inhibitor)
14 Approaches to improving therapy for ovarian cancer Apply new drugs that exploit the unique genetic susceptibilities of ovarian cancer Improving the effectiveness of existing drugs Develop new, non-chemotherapy approaches
15 Virotherapy for ovarian cancer KW Peng et al., Cancer Res. 2004
16 Virotherapy for ovarian cancer Effects of the virotherapy seen to date: 1. Direct killing of tumor cells 2. Stimulation of the immune response to the tumor
17 delivered Virotherapy for ovarian cancer - Mesenchymal cells Soon to open: Trial of measles virus delivered into the peritoneal cavity by mesenchymal stem cells. + Mesenchymal cells
18 Progress in the treatment of ovarian cancer requires a team
19 Acknowledgements Kaufmann lab Anand Patel Silvana De Lorenzo Karen Flatten Cristina Correia Poirier Lab Chantal Ethier Ovarian SPORE Cores Kim Kalli Linda Murphy Dan Visscher Ann Obserg Lynn Hartmann Phase I Program/Ovarian Group Mike Menefee Harry Long Paul Haluska Julian Molina Aminah Jatoi Andrea Wahner Hendrickson Matt Block Support from: NIH: R01 CA73709, P50 CA136393
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