PARP Inhibitors in the Management of Ovarian Cancer

Publication Date: September 23, 2022
Last Updated: January 22, 2024

Treatment

Repeating PARPi

Recommendation 1.0

Repeating PARPi therapy in the treatment of epithelial ovarian cancer (EOC) is NOT recommended at this time. Consideration should be made as to the best time in the life cycle of an individual patient’s EOC in which to use PARPi. Clinical trial participation is encouraged. ( IC , Ins , B , S )
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Newly Diagnosed Ovarian Cancer

Recommendation 2.0

PARPi are NOT recommended for use in initial treatment of early stage (stage I-II) EOC, since there is insufficient evidence to support use in this population. ( IC , Ins , B , S )
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Rapid Update – Recommendation 2.1

Patients with newly diagnosed stage III–IV EOC who are in complete or partial response to first-line platinum-based chemotherapy should be offered PARPi maintenance therapy in high-grade serous (HGS) or endometrioid ovarian cancer. For those with germline or somatic pathogenic or likely pathogenic variants in BRCA1 or BRCA2 genes, options should include olaparib (300 mg orally every 12 hours for 2 years), niraparib (200–300 mg orally daily for 3 years) or rucaparib (600 mg twice a day for 2 years). Longer duration could be considered in selected individuals after discussion of risks. For those who are HRD positive, determined using FDA-approved companion diagnostic tests, rucaparib and niraparib are options. Niraparib or rucaparib may be offered for non-BRCAmut/HRDneg patients. ( EB , H , B , S )
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Recommendation 2.2

The addition of olaparib to bevacizumab maintenance may be offered to patients who have stage III–IV high grade serous or endometrioid ovarian cancer and germline or somatic pathogenic or likely pathogenic variants in BRCA1 or BRCA2 genes and/or genomic instability, as determined by Myriad myChoice® CDx, and who have had a partial or complete response to chemotherapy + bevacizumab combination. ( EB , H , B , S )
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Recommendation 2.3

Inclusion of the PARPi, veliparib, with combination chemotherapy followed by veliparib maintenance therapy cannot be recommended at this time. There are no data that this approach is superior, equal, or less toxic than a switch maintenance. ( EB , I , , S )
Note: As of this writing, veliparib is not commercially available.

(B/H ratio unknown)

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Recurrent Ovarian Cancer - Second-line or Greater Maintenance and Treatment

Rapid Update – Recommendation 3.0

PARPi monotherapy maintenance (second-line or more) may be offered to patients with EOC who have not already received a PARPi and who have responded to platinum-based therapy regardless of BRCA mutation status; treatment is continued until progression of disease or toxicity despite dose reductions and best supportive care. ( EB , H , B , S )
  • Options include: olaparib 300 mg every 12 hours, rucaparib 600 mg every 12 hours or niraparib 200–300 mg once daily.
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Maintenance treatment with niraparib for patients without germline or somatic BRCA mutation should weigh potential PFS benefit against possible overall survival decrement. ( EB , L , B , M )
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Rapid Update – Recommendation 3.1/3.2

PARPi monotherapy should not be routinely offered to patients for the treatment of recurrent platinum sensitive EOC. ( EB , I , B , M )
Evidence on PARPi use in this setting is evolving and data are continuing to emerge. Any decision to proceed with PARPi treatment in select populations (BRCA mutation, No prior PARPi use, Platinum Sensitive, Advanced Lines of Treatment) should be based on individualized patient and provider assessment of risks, benefits, and preferences.
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Rapid Update – Recommendation 3.3

PARPi monotherapy is NOT recommended for treatment for patients with either BRCA wild-type or platinum-resistant recurrent EOC. ( EB , H , B , S )
This rapid recommendation update provides timely guidance on the use of rucaparib based on the results of the ARIEL4 trial, as well as the use of olaparib (SOLO3 trial) and niraparib (ENGOT-OV16/NOVA trial).
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PARPi in Combination

Recommendation 4.0

PARPi are NOT recommended for use in combination with chemotherapy, other targeted agents, or immune-oncology agents in the recurrent setting outside the context of a clinical trial. Clinical trial participation is encouraged. ( IC , Ins , B , S )
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Management of Adverse Events


Recommendation 5.0 Anemia

a. Patients requiring a blood transfusion for symptom relief and/or hemoglobin below 8g/dl should be monitored. PARPi dose should be reduced with evidence of repeat anemia in order to avoid multiple transfusions. (, , , )
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b. Patients with progressive anemia may be offered growth factor per ASCO guidelines and physician and patient comfort. (IC, B, M, Ins)
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Recommendation 5.1 Neutropenia:

a. Growth factor is NOT indicated for use in patients receiving daily PARPi. (, , , )
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b. Neutropenia (grade 4 lasting at least 5–7 days or associated with fever) should result in dose hold until recovery of infection and granulocyte count, followed by dose reduction. Growth factor support may be used in this setting to support patient safety during the drug hold.
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Recommendation 5.2 Platelets:

a. Thrombocytopenia is most common with niraparib. Niraparib dosing guidelines should be used to lower starting dose (200 mg) based on weight and platelet count. (, , , )
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b. Discontinue PARPi for persistent thrombocytopenia or significant bleeding despite dose reduction. (IC, B, M, Ins)
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Recommendation 5.3 Persistent cytopenia:

Evaluation for treatment-related myelodysplastic syndromes and acute myeloid leukemia (MDS/AML) should be initiated in patients with persistent cytopenia that occurs despite drug hold. (IC, B, M, Ins)
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Recommendation 5.4 Nausea:

a. Many patients will have tachyphylaxis of nausea symptoms over the first cycle of therapy. (, , , )
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b. Persistent nausea requiring daily anti-emetic intervention, causing a reduction in performance status, and/or resulting in more than a 5% weight loss should result in dose reduction. (IC, B, M, Ins)
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Recommendation Grading

Overview

Title

PARP Inhibitors in the Management of Ovarian Cancer

Authoring Organization

Publication Month/Year

September 23, 2022

Last Updated Month/Year

February 1, 2024

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Female, Adolescent, Adult, Older adult

Health Care Settings

Ambulatory, Hospital, Outpatient, Radiology services

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Treatment, Management

Diseases/Conditions (MeSH)

D010051 - Ovarian Neoplasms, D010049 - Ovarian Diseases, D010048 - Ovarian Cysts, D000077216 - Carcinoma, Ovarian Epithelial, D000071137 - Poly (ADP-Ribose) Polymerase-1

Keywords

ovarian cancer, Epithelial Ovarian Cancer, Advanced Ovarian Cancer, PARP Inhibitors, PARP

Source Citation

Tew W, Lacchetti C, Kohn E, et al. PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. [published online ahead of print, 2022 Sep 23]. doi: 10.1200/JCO.20.01934

Tew W, Lacchetti C, Ellis A, et al. PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline. J Clin Oncol. 2020;38(30):3468-3493. doi:10.1200/jco.20.01924

Supplemental Methodology Resources

Data Supplement, Evidence Tables

Methodology

Number of Source Documents
54
Literature Search Start Date
January 1, 2009
Literature Search End Date
September 13, 2022