Kimberly Halla, MSN, FNP-C, Paula J. Anastasia, RN, MN, AOCN, and Nelli Zafman, MSN, CRNP, AOCNP prepared useful Practice Aids pertaining to PARP inhibitor therapy for this CNE activity titled, "Realizing the Promise of PARP Inhibitors in Solid Tumor Therapy: Guiding Oncology Nurses on the Advances and Challenges." For the full presentation, monograph, complete CNE information, and to apply for credit, please visit us at http://bit.ly/2EkO5Ij. CNE credit will be available until May 22, 2020.

1. A Guide to PARP Inhibitors in the Clinic:
Current Indications and Ongoing Research
PRACTICE AID
Access the activity, “Realizing the Promise of PARP Inhibitors in Solid Tumor Therapy: Guiding Oncology Nurses
on the Advances and Challenges,” at PeerView.com/KWE40.
Current FDA-Approved PARP Inhibitors in Ovarian Cancer
• Indicated in pts with gBRCAm advanced disease
previously treated with ≥3 chemotherapies;
• Companion diagnostic1
: BRCA1/2 testing using
BRACAnalysis CDxR
Study 42 in 193 pts2
ORR: 31%
Ongoing Phase 3 SOLO-33
: Olaparib vs
chemotherapy in platinum-sensitive, relapsed
ovarian cancer pts with gBRCA1/2m
Study 195
• Indicated as maintenance tx in pts with
gBRCAm or sBRCAm advanced disease
following response to first-line
platinum-based chemotherapy
• Companion diagnostic1
: BRCA1/2 testing
using BRACAnalysis CDxR
• Indicated as maintenance tx in pts receiving
≥2 prior chemotherapies and achieving
CR or PR to the previous
platinum-based regimen
• No companion diagnostic
Olaparib
Phase 3 SOLO-24
: Olaparib vs placebo
in 295 BRCAmut
pts in CR or PR after ≥2 prior
platinum regimens
Phase 3 SOLO-16
: Olaparib vs placebo
as a first-line maintenance regimen in 391 pts
achieving CR or PR following first-line standard
platinum-based chemotherapy
Median PFS: 19.1 vs 5.5 mo; HR = 0.30; P < .0001
Median PFS: NR vs 13.8 mo; HR = 0.30; P < .001
• Indicated in pts with gBRCAm or sBRCAm
advanced disease previously treated with
≥2 chemotherapies
• Companion diagnostic1
: BRCA1/2 testing using
BRACAnalysis CDxR or next-gen sequencing
using FoundationFocus™ CDx BRCA
BRCAmut
pts. ORR: 69%; Median PFS: 12.8 mo
(HR [vs BRCAwt
/LOHlow
] = 0.25; P < .001)
BRCAwt
/LOHhigh
pts. ORR: 30%; Median PFS:
7.2 mo (HR [vs BRCAwt
/LOHlow
] = 0.51; P < .001)
BRCAwt
/LOHlow
pts. ORR: 13%; Median PFS: 5.0 mo
Study 109
Rucaparib
Phase 2 ARIEL-27,8
: Rucaparib vs placebo in
192 pts with platinum-sensitive, relapsed,
high-grade serous or endometrioid ovarian
cancers receiving ≥1 prior platinum chemotherapy
Agent Indications Supporting Trials Key Results/Ongoing Studies
• Indicated as maintenance tx in patients
receiving ≥2 prior chemotherapies and
achieving CR or PR to the previous
platinum-based regimen
• No companion diagnostic
BRCAmut
pts. Median PFS: 16.6 vs 5.4 mo;
HR = 0.23; P < .0001
HRD+ pts. Median PFS: 13.6 vs 5.4 mo;
HR = 0.32; P < .0001
Intent-to-treat pts. Median PFS: 10.8 vs 5.4 mo;
HR = 0.36; P < .0001
Ongoing Phase 3 ARIEL-411
: Rucaparib versus
platinum-based chemotherapy in BRCAmut
pts
with relapsed high grade epithelial ovarian,
fallopian tube, or primary peritoneal cancer
Phase 3 ARIEL-310
: Rucaparib vs placebo
after ≥2 prior platinum regimens in
high-grade serous or endometrioid
ovarian cancer pts achieving CR or PR
to previous platinum-based regimen

2. A Guide to PARP Inhibitors in the Clinic:
Current Indications and Ongoing Research
PRACTICE AID
Access the activity, “Realizing the Promise of PARP Inhibitors in Solid Tumor Therapy: Guiding Oncology Nurses
on the Advances and Challenges,” at PeerView.com/KWE40.
Agent Indications Supporting Trials Key Results/Ongoing Studies
• Indicated as maintenance tx following response
to platinum-based chemotherapy in pts
with or without a BRCA mutation receiving
≥2 prior platinum-based regimens
• No companion diagnostic
BRCAmut
pts. Median PFS: 21.0 vs 5.5 mo;
HR = 0.27; P < .0001
Non-gBRCAm pts. Median PFS: 9.3 vs 3.9 mo;
HR = 0.45; P < .0001
Non-gBRCAm HRD+ pts. Median PFS: 12.9 vs
3.8 mo; HR = 0.38; P < .0001
Ongoing Phase 3 PRIMA13
: Niraparib vs placebo
as first-line maintenance regimen in pts achieving
CR or PR following first-line standard
platinum-based chemotherapy; N = 727
• Safety results: Individualized dosing
was much better tolerated than the fixed
dosing schedule
Niraparib
Phase 3 NOVA12
: Niraparib vs placebo
in pts achieving CR or PR after ≥2 prior
platinum regimens;
gBRCAm N = 203; Non-gBRCAm, incl. sBRCAm,
HRD+, HRD- N = 350
Agent Indications Supporting Trials Key Results/Ongoing Studies
• Indicated in patients with gBRCAm,
HER2-negative, locally advanced or metastatic
breast cancer who have been treated with
chemotherapy in the neoadjuvant, adjuvant,
or metastatic setting
• Companion diagnostic1
: BRCA1/2 testing
using BRACAnalysis CDxR
Median PFS: 7.0 vs 4.2 mo; HR = 0.58; P < .001Olaparib
Phase 3 OLYMPiAD14
: Olaparib vs placebo
in pts receiving ≤2 prior lines of chemotherapy
for gBRCAm, HER2-negative advanced
breast cancer; N = 302
• Indicated in patients with gBRCAm,
HER2-negative, locally advanced or metastatic
breast cancer
• Companion diagnostic1
: BRCA1/2 testing using
BRACAnalysis CDxR
Talazoparib
Phase 3 EMBRACA15
: Talazoparib vs placebo
in pts receiving ≤3 prior lines of
chemotherapy for gBRCAm, HER2-negative
advanced breast cancer; N = 431
Current FDA-Approved PARP Inhibitors in Breast Cancer
Median PFS: 8.6 vs 5.6 mo; HR = 0.54; P < .001

3. A Guide to PARP Inhibitors in the Clinic:
Current Indications and Ongoing Research
PRACTICE AID
Access the activity, “Realizing the Promise of PARP Inhibitors in Solid Tumor Therapy: Guiding Oncology Nurses
on the Advances and Challenges,” at PeerView.com/KWE40.
Key Ongoing Research on PARP Inhibitors in the Phase 3 Setting in Solid Tumors Other than Ovarian and Breast Cancers
Trial Name Trial Number Settings Patient Population
PROfound16
PROPEL17
TRITON-318
MAGNITUDE19
POLO20
NCT02987543 mCRPC
Olaparib vs AR-targeted therapy in previously-treated
pts with HRR mutation
NCT03732820 mCRPC Abiraterone/prednisone + olaparib or placebo in the
first-line tx of genetically unselected pts
NCT02975934 mCRPC
Rucaparib vs enzalutamide/abiraterone or docetaxel
in previously AR-treated pts with HRD mutations
NCT03748641 mCRPC Niraparib + abiraterone/prednisone in front-line disease
NCT02184195 Pancreatic cancer
Olaparib vs placebo in pts with gBRCA1/2m metastatic pancreatic
cancer responding to first-line platinum-based chemotherapy
AR: androgen receptor; BRCA: breast cancer gene; CR: complete response; gBRCAm: mutated germline BRCA gene; HER2: human epidermal growth factor receptor 2; HR: hazard ratio; HRD: homologous recombination DNA repair; HRR: homologous recombination repair; mCRPC: metastatic
castration-resistant prostate cancer; NR: not reached; OS: overall survival; PARP: poly(ADP)-ribose polymerase; PFS: progression-free survival; PR: partial response.
1. https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm. Accessed March 25, 2019. 2. Kaufman B et al. JClinOncol. 2015;33:244-250. 3. https://clinicaltrials.gov/ct2/show/NCT02282020. Accessed March 25, 2019. 4. Pujade-Lauraine E et al. Lancet
Oncol. 2017;18:1274-1284. 5. https://clinicaltrials.gov/ct2/show/NCT00753545. Accessed March 25, 2019. 6. Moore K et al. NEnglJMed.2018; 379:2495-2505. 7. Coleman R et al. American Society of Clinical Oncology 2016 Annual Meeting (ASCO 2016). Abstract 5540. 8. Swisher EM et al. LancetOncol.
2017;18:75-87. 9. https://clinicaltrials.gov/ct2/show/NCT01482715. Accessed March 25, 2019. 10. Coleman RL et al. Lancet.2017;390:1949-1961. 11. https://clinicaltrials.gov/ct2/show/NCT02855944. Accessed March 25, 2019. 12. Mirza MR et al.NEnglJMed. 2016;375:2154-2164. 13. Gonzalez A et al. Ann
Oncol. 2018; 29 (suppl_8): Abstract 941PD. 14. Robson M et al. NEnglJMed. 2017;377:523-533. 15. Litton JK et al. NEnglJMed. 2018;379:753-763. 16. https://clinicaltrials.gov/ct2/show/NCT02987543. Accessed March 25, 2019. 17. https://clinicaltrials.gov/ct2/show/NCT03732820. Accessed March 25, 2019.
18. https://clinicaltrials.gov/ct2/show/NCT02975934. Accessed March 25, 2019. 19. https://clinicaltrials.gov/ct2/show/NCT03748641. Accessed March 25, 2019. 20. https://clinicaltrials.gov/ct2/show/NCT02184195. Accessed March 25, 2019.
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice.

4. PARP Inhibitors: General Guidance for Nursing Management
PRACTICE AID
Access the activity, “Realizing the Promise of PARP Inhibitors in Solid Tumor Therapy: Guiding Oncology Nurses
on the Advances and Challenges,” at PeerView.com/KWE40.
Genetic Testing/Counseling1
Which patients with ovarian cancer should I test for BRCA1/2 mutations?
• All patients with ovarian cancer (EOC), peritoneal cancer (PPC), and fallopian tube cancer (FTC)
• Insurance will cover appropriate patients
Which patients with cancers other than breast and ovarian should I test for BRCA1/2 mutations?
Patients with:
• Pancreatic or prostate cancer (Gleason score ≥7) and with
– ≥1 relative with breast cancer (aged ≤50 y) or ovarian cancer (any age)
– 2 relatives with breast cancer (any age), pancreatic cancer, or prostate cancer
• Pancreatic cancer patients who have Ashkenazi Jewish history
• A family history of BRCA1/2 mutations
• A somatic BRCA1/2 mutation identified in the tumor
Which patients with breast cancer should I test for BRCA1/2 mutations?
Patients with or who are:
• Aged ≤45 y, or ≤50 y if from a small family with few women
• TNBC, aged ≤60 y
• Ashkenazi Jewish history
• Male
• Bilateral breast cancer, with the first appearance when the patient was aged ≤50 y
• Aged ≤50 y with ≥1 relative with breast, pancreatic, or prostate cancer
• Any age with
– ≥2 relatives with breast, pancreatic, or prostate cancer
– ≥1 relative with ovarian cancer
– ≥1 relative with breast cancer diagnosed when aged ≤50 y
– ≥1 male relative with breast cancer

5. PARP Inhibitors: General Guidance for Nursing Management
PRACTICE AID
Access the activity, “Realizing the Promise of PARP Inhibitors in Solid Tumor Therapy: Guiding Oncology Nurses
on the Advances and Challenges,” at PeerView.com/KWE40.
FDA-Approved PARP Inhibitors: Dosing, AEs, and Other Considerations2-5
What is the recommended dosing for olaparib?
• Tablets: 300 mg orally twice daily with or without food
• Guidance for management:
– Continue treatment until disease progression or unacceptable toxicity. Firstline maintenance continued
up to 2 years in patients achieving CR
– For adverse reactions, consider dose interruption or dose reduction
– For moderate renal impairment (ClCr 31-50 mL/min), reduce dose to 200 mg twice daily
What is the recommended dosing for niraparib?
• Capsules: 300 mg orally once daily with or without food
• Guidance for management:
– Continue treatment until disease progression or unacceptable toxicity
– For adverse reactions, consider interruption of treatment, dose reduction, or dose discontinuation
What is the recommended dosing for rucaparib?
• Tablets: 600 mg orally twice daily with or without food
• Guidance for management:
– Continue treatment until disease progression or unacceptable toxicity
– For adverse reactions, consider interruption of treatment or dose reduction
What is the recommended dosing for talazoparib?
• Capsules: 1 mg taken as a single oral daily dose with or without food
• Guidance for management:
– Continue treatment until disease progression or unacceptable toxicity
– For adverse reactions, consider dose interruption or dose reduction
– For moderate renal impairment (ClCr 30-59 mL/min), recommended dose is 0.75 mg once daily

6. PARP Inhibitors: General Guidance for Nursing Management
PRACTICE AID
Access the activity, “Realizing the Promise of PARP Inhibitors in Solid Tumor Therapy: Guiding Oncology Nurses
on the Advances and Challenges,” at PeerView.com/KWE40.
Which adverse events should I monitor my patients for with olaparib?
• Warnings and Precautions: MDS/AML (<1.5%), pneumonitis, embryo-fetal toxicity
• Most common AEs (≥20%) in clinical trials: anemia, nausea, fatigue (including asthenia), vomiting, neutropenia,
leukopenia, nasopharyngitis/URTI/influenza, respiratory tract infection, diarrhea, arthralgia/myalgia, dysgeusia,
headache, dyspepsia, decreased appetite, constipation, and stomatitis
• Most common laboratory abnormalities (≥25%): decrease in hemoglobin, increase in mean corpuscular volume,
decrease in lymphocytes, decrease in leukocytes, decrease in absolute neutrophil count, increase in serum creatinine,
and decrease in platelets
Which adverse events should I monitor my patients for with niraparib?
• Warnings and Precautions: MDS/AML, bone marrow suppression, CV effects, embryo-fetal toxicity
• Most common AEs (≥10%) in clinical trials: thrombocytopenia, anemia, neutropenia, leukopenia, palpitations,
nausea, constipation, vomiting, abdominal pain/distention, mucositis/stomatitis, diarrhea, dyspepsia, dry mouth,
fatigue/asthenia, decreased appetite, UTI, AST/ALT elevation, myalgia, back pain, arthralgia, headache, dizziness,
dysgeusia, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash, and hypertension
Which adverse events should I monitor my patients for with rucaparib?
• Warnings and Precautions: MDS/AML, embryo-fetal toxicity
• Most common AEs (≥20%) in clinical trials: nausea, fatigue (including asthenia), vomiting, anemia, abdominal pain,
dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, and dyspnea
• Mostcommonlaboratoryabnormalities(≥25%): increase in creatinine, increase in ALT, increase in AST, decrease in
hemoglobin,decreaseinlymphocytes,increaseincholesterol,decreaseinplatelets,anddecreaseinabsoluteneutrophilcount
Which adverse events should I monitor my patients for with talazoparib?
• Warnings and Precautions: MDS/AML, myelosuppression, and embryo-fetal toxicity
• Most common AEs (≥20%) in clinical trials: fatigue, anemia, nausea, neutropenia, headache, thrombocytopenia,
vomiting, alopecia, diarrhea, and decreased appetite
• Most common laboratory abnormalities (≥25%): decrease in hemoglobin, platelets, neutrophils, lymphocytes,
leukocytes, and calcium; increases in glucose, ALT, AST, and ALP

7. PARP Inhibitors: General Guidance for Nursing Management
PRACTICE AID
Access the activity, “Realizing the Promise of PARP Inhibitors in Solid Tumor Therapy: Guiding Oncology Nurses
on the Advances and Challenges,” at PeerView.com/KWE40.
How should I monitor and treat my patients for MDS?
• Check CBC/d prior to starting PARP inhibitor and monthly thereafter (olaparib, rucaparib, talazoparib)
• Check CBC/d weekly for 1 mo, then monthly for the next 11 mo, and longer as needed (niraparib)
• If hematological toxicities are noted
– Interrupt PARP inhibitor and monitor blood counts weekly until grade ≤1
– If hematological profile recovers, consider restarting drug at reduced dose; if profile has not recovered to grade ≤1
after 4 wk, refer to hematologist for bone marrow analysis and cytogenetics
– Discontinue drug if MDS/AML is confirmed
What is important for me to know when managing AEs?
• Thorough assessments are valuable for identifying and managing AEs
• Patients may not be forthcoming in reporting AEs
• Monitor lab values, including CBC and CMP
• Although oral agents are taken at home, they are active medications that require close surveillance
• Educate patients about what to look for; encourage communication as issues arise
What is important for my patient to understand about managing AEs?
• Discuss with the patient that even though this is an oral agent, there will be AEs
• Discuss the importance of compliance and possible challenges
• Maintain regular follow-up and communication
• Encourage use of tools (calendar, medication box, reminders) to help patients manage therapy
AE: adverse event; ALP: alkaline phosphatase; ALT: alanine transaminase; AST: aspartate transaminase; BRCA: breast cancer gene; CBC: complete blood count; CBC/d: CBC with differential; ClCr: creatinine clearance; CMP: comprehensive metabolic panel; CR: complete response; gBRCAm: mutated
germline BRCA gene; MDS/AML: myelodysplastic syndromes / acute myeloid leukemia; PARP: poly(ADP)-ribose polymerase; PR: partial response; TNBC: triple-negative breast cancer; URTI: upper respiratory tract infection; UTI: urinary tract infection.
1. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Genetic/Familial High-Risk Assessment: Breast and Ovarian. Version 3.2019. https://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf. Accessed March 20, 2019. 2. Lynparza (olaparib
tablets) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208558s001lbl.pdf. Accessed March 20, 2019. 3. Rubraca (rucaparib) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/209115s000lbl.pdf. Accessed March 20, 2019.
4. Zejula (niraparib) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208447lbl.pdf. Accessed March 20, 2019. 5. Talzenna (talazoparib) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211651s000lbl.pdf. Accessed March 20, 2019.
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice.