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

2. 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 that were presented in abstract form. These data should be considered preliminary until published in a peer-reviewed journal.

3. Poly(ADP-ribose) Polymerases

4. PARP Involvement in DNA Repair

5. Challenges to the Model

6. Alternative Models of PARP Inhibition

7. Alternative Models of PARP Inhibition (cont)

8. PARP Inhibitors

9. Differences Among PARP Inhibitors

10. Single Agent Development

11. "Study 42": Single Agent Olaparib

12. Talazoparib Phase 1

13. Talazoparib Phase 2 (ABRAZO)

14. OlympiAD Study Design

15. Primary Endpoint: PFS by BICR

16. Objective Response by BICR

17. Adverse Events (Any Grade) in ≥15% of Patients

18. BROCADE Trial Design

19. BROCADE Trial: Tumor Response

20. BROCADE Trial: PFS

21. Phase 1 Trial of Olaparib and Cisplatin

22. PARP Inhibitor With PI3K Inhibitor for BRCA1-Related Breast Cancer

23. OlympiA: Olaparib in High-Risk Germline BRCA Mutations

24. Possible Role of PARP Inhibitor Therapy in Other Settings

25. Mechanisms of Resistance

26. Platinum Cross-Resistance?

27. Conclusions and Summary

28. Abbreviations

29. Abbreviations (cont)

30. Abbreviations (cont)