PARP inhibitors work by disabling DNA base excision repair, which normally fixes DNA damage caused by chemotherapy agents like platinum. When PARP is inhibited, single-strand DNA breaks caused by chemotherapy cannot be repaired, and instead cause double-strand breaks during DNA replication. This ultimately leads to cell death in cancer cells. PARP inhibitors are particularly effective for cancers with defects in homologous recombination repair genes like BRCA1 and BRCA2, as these cancers rely more heavily on PARP-mediated repair. Several PARP inhibitors are approved or in clinical trials for ovarian cancer, breast cancer, prostate cancer, and other solid tumors.

1. Molecular Mechanism
of PARP Inhibition1,2
Access the activity, “Advances in Precision Care in Solid Tumor Oncology:
Defining the Role of PARP Inhibitors,” at PeerView.com/RKN40.
PRACTICE AID
BRCA: breast cancer gene; NAD: nicotinamide adenine dinucleotide; PAR: poly (ADP-ribose); PARG: PAR glycohydrolase; PARP: poly (ADP-ribose) polymerase; Pt: platinum.
1. Adapted from O’Shaughnessy J et al. 2009 American Society of Clinical Oncology Annual Meeting (ASCO 2009). Abstract 3.
2. Adapted from Toss A, Cortesi L. J Cancer Sci Ther. 2013;5:409-416.
Pt
Pt
Pt
Pt
PARP
PARP
PARP
upregulation
Base-excision
repair of DNA
damage
Platinum
chemotherapy
Inflicts DNA
damage via
adducts and
DNA
crosslinking
Inhibition
of PARP
Disables DNA
base-excision
repair
Recombination repair
Replication
fork collapse
Double-strand
DNA break
Cell deathCell survival
PARPDNA damage
NAD+
Nicotinamide
+ PAR
BRCA1
BRCA2
PARP
inhibitor
PARG
Repair enzymes
Chains
of
PAR
Pt

2. Selected, Recruiting
Phase 3 Clinical Trials
of PARP Inhibitors
Access the activity, “Advances in Precision Care in Solid Tumor Oncology:
Defining the Role of PARP Inhibitors,” at PeerView.com/RKN40.
PRACTICE AID
NCT035192301
Ovarian Cancer
Pamiparib vs placebo
Patients with platinum-sensitive
recurrent ovarian cancer;
Planned N = 216
Primary endpoint: PFS
NCT03522246
(ATHENA)2
Rucaparib + nivolumab as
maintenance therapy following
front-line platinum-based
chemotherapy
Patients with newly diagnosed
ovarian cancer; Planned N = 1,012
Primary endpoint:
Investigator-assessed PFS
NCT02855944
(ARIEL-4)3
Rucaparib vs chemotherapy
Patients with BRCA-mutant,
relapsed, high-grade epithelial
ovarian, fallopian tube, or
primary peritoneal cancer;
Planned N = 345
Primary endpoint:
Investigator-assessed PFS
by RECIST 1.1
NCT03740165
(KEYLYNK-001)4
Carboplatin/paclitaxel +
pembrolizumab and
maintenance olaparib
as a first-line therapy
Patients with BRCAnonmutated
advance EOC, fallopian tube
cancer, or primary peritoneal
cancer; Planned N = 620
Primary endpoint: PFS and OS
NCT037376435
Durvalumab + chemotherapy +
bevacizumab and maintenance
durvalumab + bevacizumab +
olaparib
Patients with newly diagnosed,
stage III or IV nonmucinous
ovarian cancer; Planned N = 912
Primary endpoint: PFS
NCT025022666
Olaparib + cediranib maleate
vs standard chemotherapy
Patients with recurrent
platinum-resistant/platinum-
refractory ovarian, fallopian tube,
or primary peritoneal cancer;
Planned N = 680
Primary endpoint: PFS and OS
NCT03602859
(FIRST)7
Ovarian Cancer (Cont’d) Breast Cancer
Niraparib vs standard-of-care
platinum-based therapy
as first-line therapy
Patients with mCRPC who have
not received prior chemotherapy
or NHAs for mCRPC;
Planned N = 720
Primary endpoint: PFS
NCT03598270
(ANITA)8
Platinum-based therapy +
atezolizumab + niraparib
Patients with recurrent ovarian,
tubal, or peritoneal cancer and
a platinum-treatment interval
>6 mo; Planned N = 414
Primary endpoint: PFS
NCT025022669
Olaparib + platinum-based
chemotherapy as neoadjuvant
therapy
Patients withTNBC and/or gBRCA
breast cancer; Planned N = 527
Primary endpoint: N withTEAEs,
pCR rate + completion rate of
olaparib, and pCR at surgery after
neoadjuvant therapy

3. Selected, Recruiting
Phase 3 Clinical Trials
of PARP Inhibitors
Access the activity, “Advances in Precision Care in Solid Tumor Oncology:
Defining the Role of PARP Inhibitors,” at PeerView.com/RKN40.
PRACTICE AID
Prostate Cancer
NCT03395197
(TALAPRO-2)12
Talazoparib + enzalutamide
vs enzalutamide + placebo
Patients with assessment of
DDR mutation status; metastatic
disease in bone, ECOG PS 0 or 1;
Planned N = 1,037
Primary endpoint:
Confirm dose of talazoparib;
radiographic PFS
NCT02975934
(TRITON3)11
Rucaparib vs abiraterone,
enzalutamide, or docetaxel
Patients with mCRPC associated
with homologous recombination
deficiency; Planned N = 400
Primary endpoint:
Radiographic PFS
NCT03732820
(PROPEL)13
Prostate Cancer (Cont’d) Gastric Cancer
Olaparib or placebo +
abiraterone/prednisone
as first-line therapy
Patients with mCRPC who have
not received prior chemotherapy
or NHAs for mCRPC;
Planned N = 720
Primary endpoint:
Radiographic PFS
NCT03834519
(KEYLYNK-010)14
Olaparib + pembrolizumab
vs abiraterone acetate
or enzalutamide
Patients with mCRPC who have
failed to respond to either
abiraterone acetate or
enzalutamide (but not both)
and to chemotherapy;
Planned N = 780
Primary endpoint:
OS and radiographic PFS
NCT0342781415
Pamiparib (BGB-290)
vs placebo
Patients with previously treated
advanced or inoperable gastric
cancer who have responded to
first-line platinum therapy;
Planned N = 540
Primary endpoint: PFS
NCT03748641
(MAGNITUDE)10
Niraparib + abiraterone/
prednisone in front-line disease
Patients with mCRPC;
Planned N = 1,000
Primary endpoint:
Radiographic PFS
Lung Cancer
NCT03976362
(KEYLYNK-008)16
Pembrolizumab with or
without maintenance olaparib
as first-line therapy
Patients with metastatic,
squamous non–small cell
lung cancer; Planned N = 735
Primary endpoint:
PFS per RECIST 1.1 and OS
NCT03976323
(KEYLYNK-006)17
Pembrolizumab with
maintenance olaparib or
pemetrexed as first-line therapy
Patients with metastatic,
nonsquamous non–small cell
lung cancer; Planned N = 792
Primary endpoint:
PFS per RECIST 1.1 and OS
NCT0351608418
Niraparib as maintenance
therapy following first-line
platinum-based chemotherapy
Patients with extensive-stage
disease small cell lung cancer;
Planned N = 591
Primary endpoint:
BICR-assessed PFS and OS

4. Selected, Recruiting
Phase 3 Clinical Trials
of PARP Inhibitors
Access the activity, “Advances in Precision Care in Solid Tumor Oncology:
Defining the Role of PARP Inhibitors,” at PeerView.com/RKN40.
PRACTICE AID
Ovarian Cancer
Selected Active, Not RecruitingTrials of PARP Inhibitors
NCT02655016
(FIRST)21
Niraparib as maintenance
therapy
Patients with advanced ovarian
cancer following response on
front-line platinum-based
therapy; N = 620
NCT03642132
(JAVELIN OVARIAN PARP 100)20
Avelumab + chemotherapy
followed by avelumab +
talazoparib as maintenance
therapy
Patients with previously
untreated advanced ovarian
cancer; N = 79
NCT0216369422
Breast Cancer Lung Cancer
Veliparib vs placebo in
combination with carboplatin
+ paclitaxel
Patients with HER2-negative,
metastatic or locally advanced,
unresectable, BRCA-associated
breast cancer; N = 513
NCT0203227723
Veliparib + carboplatin vs
standard chemotherapy +
carboplatin + standard
chemotherapy
Patients with early stageTNBC;
N = 634
NCT0226499024
Veliparib + carboplatin +
paclitaxel vs investigator’s
choice of standard
chemotherap
Patients receiving first cytotoxic
chemotherapy for metastatic or
advanced NSq NSCLC + who are
current/former smokers; N = 595
NCT02470585
(VELIA)19
Veliparib with carboplatin +
paclitaxel ± continuation
maintenance veliparib
Patients with previously
untreated stages III or IV
high-grade serous EOC,
fallopian tube, or primary
peritoneal cancer; N = 1,140
NCT0215298225
Temozolomide with or
without veliparib
Patients with newly diagnosed
glioblastoma multiforme;
N = 440
NCT02184195
(POLO)26
Olaparib vs placebo as
maintenance monotherapy
Patients with gBRCA-mutated,
metastatic pancreatic cancer
whose disease has not progressed
on first-line platinum-based
chemotherapy; N = 154
NCT02987543
(PROfound)27
Olaparib vs enzalutamide
or abiraterone acetate
Patients with mCRPC who have
failed prior treatment with an
NHA and have HRR gene
mutations; N = 340
Prostate CancerPancreatic CancerGlioblastoma
Ovarian Cancer
Selected Active, Not RecruitingTrials of PARP Inhibitors
NCT02655016
(FIRST)21
Niraparib as maintenance
therapy
Patients with advanced ovarian
cancer following response on
front-line platinum-based
therapy; N = 620
NCT03642132
(JAVELIN OVARIAN PARP 100)20
Avelumab + chemotherapy
followed by avelumab +
talazoparib as maintenance
therapy
Patients with previously
untreated advanced ovarian
cancer; N = 79
NCT0216369422
Breast Cancer Lung Cancer
Veliparib vs placebo in
combination with carboplatin
+ paclitaxel
Patients with HER2-negative,
metastatic or locally advanced,
unresectable, BRCA-associated
breast cancer; N = 513
NCT0203227723
Veliparib + carboplatin vs
standard chemotherapy +
carboplatin + standard
chemotherapy
Patients with early stageTNBC;
N = 634
NCT0226499024
Veliparib + carboplatin +
paclitaxel vs investigator’s
choice of standard
chemotherap
Patients receiving first cytotoxic
chemotherapy for metastatic or
advanced NSq NSCLC + who are
current/former smokers; N = 595
NCT02470585
(VELIA)19
Veliparib with carboplatin +
paclitaxel ± continuation
maintenance veliparib
Patients with previously
untreated stages III or IV
high-grade serous EOC,
fallopian tube, or primary
peritoneal cancer; N = 1,140
NCT0215298225
Temozolomide with or
without veliparib
Patients with newly diagnosed
glioblastoma multiforme;
N = 440
NCT02184195
(POLO)26
Olaparib vs placebo as
maintenance monotherapy
Patients with gBRCA-mutated,
metastatic pancreatic cancer
whose disease has not progressed
on first-line platinum-based
chemotherapy; N = 154
NCT02987543
(PROfound)27
Olaparib vs enzalutamide
or abiraterone acetate
Patients with mCRPC who have
failed prior treatment with an
NHA and have HRR gene
mutations; N = 340
Prostate CancerPancreatic CancerGlioblastoma
BRCA: breast cancer gene; CR: complete response; EOC: epithelial ovarian cancer; gBRCAm: mutated germline BRCA gene; NHA: new hormonal agent; NSCLC: non–small cell lung cancer; NSq: nonsquamous;
ORR: overall response rate; PFS: progression-free survival.
1. https://clinicaltrials.gov/ct2/show/NCT03519230. Accessed September 26, 2019. 2. https://clinicaltrials.gov/ct2/show/NCT03522246. Accessed September 26, 2019. 3. https://clinicaltrials.gov/ct2/show/
NCT02855944. Accessed September 26, 2019. 4. https://clinicaltrials.gov/ct2/show/NCT03740165. Accessed September 26, 2019. 5. https://clinicaltrials.gov/ct2/show/NCT03737643. Accessed
September 26, 2019. 6. https://clinicaltrials.gov/ct2/show/NCT02502266. Accessed September 26, 2019. 7. https://clinicaltrials.gov/ct2/show/NCT03602859. Accessed September 26, 2019.
8. https://clinicaltrials.gov/ct2/show/NCT03598270. Accessed September 26, 2019. 9. https://clinicaltrials.gov/ct2/show/NCT03150576. Accessed September 26, 2019. 10. https://clinicaltrials.gov/ct2/show/
NCT03748641. Accessed September 26, 2019. 11. https://clinicaltrials.gov/ct2/show/NCT02975934. Accessed September 26, 2019. 12. https://clinicaltrials.gov/ct2/show/NCT03395197. Accessed
September 26, 2019. 13. https://clinicaltrials.gov/ct2/show/NCT03732820. Accessed September 26, 2019. 14. https://clinicaltrials.gov/ct2/show/NCT03834519. Accessed September 26, 2019.
15. https://clinicaltrials.gov/ct2/show/NCT03427814. Accessed September 26, 2019. 16. https://clinicaltrials.gov/ct2/show/NCT03976362. Accessed September 26, 2019. 17. https://clinicaltrials.gov/ct2/show/
NCT03976323. Accessed September 26, 2019. 18. https://clinicaltrials.gov/ct2/show/NCT03516084. Accessed September 26, 2019. 19. https://clinicaltrials.gov/ct2/show/NCT02470585. Accessed
October 8, 2019. 20. https://clinicaltrials.gov/ct2/show/NCT03642132. Accessed October 8, 2019. 21. https://clinicaltrials.gov/ct2/show/NCT02655016. Accessed October 8, 2019. 22. https://clinicaltrials.gov/ct2/
show/NCT02163694. Accessed October 8, 2019. 23. https://clinicaltrials.gov/ct2/show/NCT02032277. Accessed October 8, 2019. 24. https://clinicaltrials.gov/ct2/show/NCT02264990. Accessed
October 8, 2019. 25. https://clinicaltrials.gov/ct2/show/NCT02152982. Accessed October 8, 2019. 26. https://clinicaltrials.gov/ct2/show/NCT02184195. Accessed October 8, 2019. 27. https://clinicaltrials.gov/ct2/
show/NCT02987543. Accessed October 8, 2019.

5. FDA-Approved
PARP Inhibitors for the
Treatment of Solid Tumors
Access the activity, “Advances in Precision Care in Solid Tumor Oncology:
Defining the Role of PARP Inhibitors,” at PeerView.com/RKN40.
PRACTICE AID
AML: acute myeloid leukemia; ALT: alanine transaminase; AST: aspartate aminotransferase; BRCA: breast cancer gene; CR: complete response; gBRCAm: mutated germline BRCA gene; HER2: human
epidermal growth factor receptor 2; MDS: myelodysplastic syndromes; PARP: poly(ADP)-ribose polymerase; PR: partial response; sBRCAm: mutated somatic BRCA gene; tx: treatment.
a
Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy.
1. https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm. Accessed September 23, 2019.
Agent
Niraparib
Indicated in patients with advanced ovarian cancer
who have been treated with ≥3 prior chemotherapy
regimens and whose cancer is associated with
homologous recombination deficiency
(HRD)–positive status
HRD status testing using
myChoice® CDx
No companion diagnostic
No companion diagnostic
BRCA1/2 testing using
BRACAnalysis CDx® or
next-gen sequencing using
FoundationOne CDx®
BRCA1/2 testing using
BRACAnalysis CDx® or
next-gen sequencing using
FoundationOne CDx®
BRCA1/2 testing using
BRACAnalysis CDx®
or next-gen sequencing using
FoundationFocus™ CDx BRCA or
FoundationOne CDx®
BRCA1/2 testing using
BRACAnalysis CDx®
BRCA1/2 testing using
BRACAnalysis CDx®
Indicated as maintenance tx in pts with gBRCAm
or sBRCAm advanced ovarian cancer following
response to first-line platinum-based chemotherapy
Indicated in pts with gBRCAm or sBRCAm
advanced ovarian cancer previously treated
with ≥2 chemotherapies
Indicated as maintenance tx in pts with
recurrent ovarian cancer, achieving CR or PR
to platinum-based chemotherapy
Indicated in pts with gBRCAm, HER2-negative,
metastatic breast cancer who have been treated
with chemotherapy in the neoadjuvant, adjuvant,
or metastatic settinga
Indicated as maintenance tx in pts with
recurrent ovarian cancer, achieving CR or PR
to platinum-based chemotherapy
Indicated in gBRCAm advanced ovarian cancer
previously treated with ≥3 chemotherapies
Indicated in pts with gBRCAm, HER2-negative,
locally advanced or metastatic breast cancer
Common AEs
Hematologic: anemia, thrombocytopenia, neutropenia, lymphocytopenia
Gastrointestinal: nausea, vomiting, diarrhea, constipation, abdominal pain,
dysgeusia, decreased appetite
Constitutional: fatigue, asthenia, dyspnea
Laboratory abnormalities: elevated creatinine, ALT, AST, and cholesterol
Serious AEs
Bone marrow suppression and MDS/AML
Lung-related: pneumonitis
Cardiovascular effects: hypertension and hypertensive crisis
Embryo-fetal toxicity
Olaparib
Rucaparib
Talazoparib
Spectrum of
Adverse Events
With PARP
Inhibitors
Indications
Companion
Diagnostic
No companion diagnostic
Indicated as maintenance tx in recurrent epithelial
ovarian cancer who are in a complete or partial
response to platinum-based chemotherapy