Program Overview Discussion Outline DNA Repair ABCs of DNA Repair DNA Repair Defects in Cancer DNA Repair Defects Can Be an Achilles Heel Synthetic Lethality and Cancer DNA Repair Defects Increased Sensitivity of ID: 751554
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Slide1
PARP and Other DNA Damage Repair Inhibitors in Solid Tumors: An UpdateSlide2
Program Overview Slide3
Discussion OutlineSlide4
DNA RepairSlide5
ABCs of DNA RepairSlide6
DNA Repair Defects in CancerSlide7
DNA Repair Defects Can Be an Achilles' HeelSlide8
Synthetic Lethality and Cancer DNA Repair DefectsSlide9
Increased Sensitivity of BRCA1-/- and
BRCA2-/-
Cells to PARP InhibitionSlide10
A Common Challenge for PARP Inhibitors: DNA Repair Pathway ComplexitySlide11
Loss of Multiple DNA Repair Genes Can Sensitize to PARP Inhibition Slide12
ConclusionsSlide13
PARP Inhibitors in the Treatment of Ovarian CancerSlide14
The Homologous Recombination Pathway: Ideal Environment for PARP Inhibitors' Success Slide15
Study 19: PFS in All Patients and According to BRCA StatusSlide16
NOVA: PFS in Patients With BRCA Mutations or Who Are HRD-PositiveSlide17
SOLO2: Key Efficacy OutcomesSlide18
SOLO2: Key Efficacy OutcomesSlide19
ARIEL 3: Investigator-Assessed PFSSlide20
SOLO 2: AEs of Any Grade Reported in ≥10% of Patients in Either ArmSlide21
NOVA: TEAEs of Any Grade Reported in ≥10% of Patients in Either ArmSlide22
Single-Agent Therapy in BRCA-Mutated Ovarian Cancer: An Alternative?Slide23
Study 42: Olaparib Monotherapyin g
BRCA-
Mutated Ovarian CancerSlide24
Study 10 and ARIEL 2: Rucaparib Monotherapy in gBRCA/s
BRCA
-Mutated Ovarian CancerSlide25
Two Strategies for the Use of PARP Inhibitors in Advanced Ovarian CancerSlide26
Where We Are Now: A Summary of Results With PARP InhibitorsSlide27
The Role of PARP Inhibitors in Breast Cancer TherapySlide28
OLYMPIAD: PFSSlide29
OLYMPIAD: Summary of AEs, All CausalitySlide30
OLYMPIAD: Additional Efficacy DataSlide31
OLYMPIAD: PFS in Relevant SubgroupsSlide32
QoL in the OLYMPIAD Trial Slide33
Veliparib in a Randomized Phase 2 Study: BROCADE 2 - Grade 3/4 TEAEs Slide34
BROCADE 2: PFSSlide35
BROCADE 2: Tumor ResponseSlide36
Neoadjuvant Veliparib in Unselected TNBC:
I-SPY2Slide37
ABRAZO Trial: Efficacy ResultsSlide38
ABRAZO: Hematologic ToxicitiesSlide39
ConclusionsSlide40
Future Directions in Targeting DDR in Cancer: Conclusions Slide41
Discussion OverviewSlide42
Multiple Malignancies Known to Associate With Homologous Recombination DDRSlide43
Clinical Response Rates by RECIST to Talazoparib 1 mg/day (Phase 2 Dose)Slide44
A Common Challenge for PARP Inhibitors: DNA Repair Pathway ComplexitySlide45
Trial Design: A Chemical Screen in mCRPC Patients With Test and Validation SetsSlide46
Clinical Trial Results (TOPARP-A): Patient CharacteristicsSlide47
Primary Endpoint Analysis: Responses to Olaparib in Sporadic mCRPCSlide48
Germline Aberrations in DNA Repair in mCRPC Slide49
Antitumor Activity of Olaparib and Association With Defects in DNA Repair GenesSlide50
Multiple Combination PossibilitiesSlide51
Other DNA Repair DefectsSlide52
ConclusionsSlide53
Conclusions (cont)Slide54
AbbreviationsSlide55
Abbreviations (cont)Slide56
Abbreviations (cont)Slide57
Abbreviations (cont)