/
PARP and Other DNA Damage Repair Inhibitors in Solid Tumors: An Update PARP and Other DNA Damage Repair Inhibitors in Solid Tumors: An Update

PARP and Other DNA Damage Repair Inhibitors in Solid Tumors: An Update - PowerPoint Presentation

ellena-manuel
ellena-manuel . @ellena-manuel
Follow
354 views
Uploaded On 2019-02-12

PARP and Other DNA Damage Repair Inhibitors in Solid Tumors: An Update - PPT Presentation

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

repair dna cancer parp dna repair parp cancer inhibitors pfs patients defects olympiad brca ovarian conclusions efficacy study trial

Share:

Link:

Embed:

Download Presentation from below link

Download Presentation The PPT/PDF document "PARP and Other DNA Damage Repair Inhibit..." is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.


Presentation Transcript

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)