MOCA Living Well: Understanding PARP Inhibitors in Ovarian Cancer

1. MOCA Living Well:Understanding PARP Inhibitors in Ovarian Cancer Andrea Wahner Hendrickson M.D. March 8, 2018

2. MOCA Living Well:Understanding PARP Inhibitors in Ovarian Cancer • How do PARP inhibitors work? • Why do they work better for some ovarian cancer over others? • How can these drugs be used? • What is the difference between maintenance and treatment? • What are some common side effects? • How can I know if these drugs are an option for me?

3. How do PARP inhibitors work?

4. Why do they work better in some tumors? • Depends on genetics • BRCA1/ BRCA2 mutations • These mutations lead to difficulty in repairing DNA damage • PARP inhibitors enhance that difficulty • Can be a germline (inherited) mutation OR a somatic (tumor only) mutation • Other changes in DNA repair • Some of these can be analyzed by tumor tests • Discuss with your physician

5. FDA Approved PARP Inhibitors

6. What is the difference between maintenance therapy and treatment? • Treatment • An initial treatment used in attempt to shrink the current tumor • Example: Carboplatin and Doxil for ovarian cancer that has come back • Maintenance therapy • Continuing to treat after completion of standard round of chemotherapy • Used to avoid or slow the cancer’s return • Slow the growth of advanced cancer after the initial treatment

7. Risk/Benefits of Maintenance Therapy • Benefits • May help keep cancer from coming back • May slow down cancer growth • Disadvantages • Side effects • Treatment cost • More doctor visits • Limited information on long term side effects and benefits for each individual

8. A few words on each of the three agents

9. LynparzaFDA Approved Indications • Maintenance therapy • Recurrent (not after first chemotherapy) • Tumor has completely or partially “responded” to the second platinum chemotherapy • All women regardless of mutations • Treatment • Germline (inherited) BRCA mutated ovarian cancer who have been treated with 3 or more prior lines of therapy

10. LynparzaMost common side effects • Nausea • Fatigue • Low red blood cell count • Vomiting • Diarrhea • Low neutrophil count

11. RubracaFDA Approved Indications • Treatment • BRCA mutation (germline (inherited) OR tumor only) • FoundationFocus CDxBRCA test • 2 or more prior therapies • Maintenance therapy • Under FDA review

12. RubracaMost common side effects • Nausea • Fatigue (including weakness) • Vomiting • Low red blood cell count • Abdominal pain • Changes in taste

13. ZejulaFDA Approved Indications • Maintenance therapy • Recurrent (not after first chemotherapy) • Tumor has partially or completely “responded” to the most recent platinum chemotherapy • All women regardless of mutations • Treatment • Currently under review

14. ZejulaMost common side effects • Nausea • Low platelet count • Fatigue • Low red blood cell count • Vomiting • Low neutrophil count

15. PARP Inhibitor Side Effects • All have a similar side effects, but some are more common and/or more severe in one versus another • All can cause AML/MDS (blood diseases) • Talk to your physician as to which may work best for you • Individuals react differently • No one right answer for everyone

16. Summary of the PARP Inhibitors

17. What is companion testing? • Test used with a drug to determine its applicability to a specific person • Often co-developed with the drug to help select or exclude patient groups for treatment • Used in the “treatment” setting • Not required in the “maintenance” setting

18. What is the benefit of PARPi maintenance? • Depends on your genetic make-up and the genetic make-up of the tumor • Most improvement seen with BRCA mutation • Least improvement (but improvement still seen) in those without any mutations or features of high DNA damage

19. Parting thoughts. . .PARP Inhibitors • 3 FDA approved drugs • Can be used as treatment or maintenance • Which to use is based on specific indication and discussion with your physician • Genetic status • Side effects • Dosing schedule