BRCA, HRR Deficiency, and PARP Inhibitors

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Presentation transcript:

BRCA, HRR Deficiency, and PARP Inhibitors

Outline

Cancer Suppression by BRCA1 and BRCA2

DNA Repair Pathways

DDR: Molecular Mechanisms

DDR as a Target in Cancer

Mechanism of Action: PARP Inhibitors (Olaparib, Rucaparib, Niraparib, Talazoparib, Veliparib)

Hereditary Cancer

Effect of PARP Inhibitors on BRCA1/2 Mutated Cells

Synthetic Lethality: Preclinical Data

Synthetic Lethality Targeting in BRCA1 or BRCA2 Mutations: Proof-of-Concept Trials with Olaparib

"BRCAness" Syndrome in Ovarian Cancer: A Case-Control Study

Why Prescribe a PARP Inhibitor After Response to Platinum-Based Chemotherapy?

Platinum-Based Chemotherapy Followed by PARP Inhibitor in Advanced Ovarian Cancer: Phase 3 Study Design

Niraparib in Advanced Ovarian Cancer: NOVA Trial

Olaparib in Advanced Ovarian Cancer: SOLO2 Trial

Rucaparib in Advanced Ovarian Cancer: ARIEL3 Trial

Platinum-Based Chemotherapy Followed by PARP Inhibitor in Advanced Ovarian Cancer: PFS and Other Parameters

PARP Inhibitors in Monotherapy in Advanced Ovarian Cancer: Study 10 and ARIEL2 (Rucaparib)

PARP Inhibitors in Monotherapy: ORR in the Efficacy Population

Phase 2 Study of Olaparib in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation (Study 42)

Study 42: Pancreatic Cancer Subgroup

POLO-1 Design

RUCAPANC Study: Phase 2 of Rucaparib in Patients With Pancreatic Cancer and a Germline or Somatic BRCA Mutation

RUCAPANC Investigator-Assessed Confirmed Responses by RECIST

OlympiAD Phase 3 Trial: Olaparib for MBC in Patients With a Germline BRCA Mutation

EMBRACA: Talazoparib in Advanced gBRCA Breast Cancer

OlympiA: Phase 3 Study of Olaparib vs Placebo as Adjuvant Treatment in gBRCA and High-Risk HER2-Negative Primary Breast Cancer

Germline Aberrations in DNA Repair in mCRPC

Conclusions

Conclusions (cont)

Abbreviations

Abbreviations (cont)

Abbreviations (cont)

Abbreviations (cont)