1. MOCA Living Well: Understanding PARP Inhibitors in Ovarian Cancer
Andrea Wahner Hendrickson M.D.
March 8, 2018
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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?
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
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
MENTION SOLO2 OLAPARIB HCRQOL life results!

8. A few words on each of the three agents

9. Lynparza FDA 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. Lynparza Most common side effects
Nausea
Fatigue
Low red blood cell count
Vomiting
Diarrhea
Low neutrophil count

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

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

13. Zejula FDA 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. Zejula Most 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
Drug
Maintenance
Treatment
Treatment Schedule
Starting dose
Lynparza (Olaparib)
Yes
Twice daily
2 tablets twice a day OR
8 capsules twice a day
Rubraca (Rucaparib) No
Zejula (Niraparib)
Once daily
3 capsules once a day

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
Drug
Companion Test
Genetic mutation tested
Lynparza (Olaparib)
BRACAnalysis CDx
BRCA1/ BRCA2 (blood)
Rubraca (Rucaparib)
FoundationFocus
CDx BRCA
BRCA1/BRCA2
(tumor)

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
gBRCA:
Other changes (HRD/LOH): 8.2
No mutations: 3

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