Last updated December 18, 2021

PARP Inhibitors in the Management of Ovarian Cancer

Recommendations

Repeating PARPi

Repeating PARPi therapy in the treatment of 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, B, S, Ins)
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Newly Diagnosed Ovarian Cancer

PARPis are not recommended for use in initial treatment of early stage (stage I-II) EOC because there is insufficient evidence to support use in this population. (IC, B, S, Ins)
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Women with newly diagnosed stage III-IV EOC that is in complete or partial response to first-line platinum-based chemotherapy should be offered PARPi maintenance therapy with olaparib (for those with germline or somatic pathogenic or likely pathogenic variants in BRCA1 or BRCA2 genes) or niraparib (all women) in high-grade serous (HGS) or endometrioid ovarian cancer.
  • PARPi maintenance therapy should consist of olaparib (300 mg orally every 12 hours for 2 years) or niraparib (200-300 mg orally daily for 3 years). Longer duration could be considered in selected individuals.
(EB, B, S, H)
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The addition of olaparib to bevacizumab maintenance may be offered to patients who have stage III-IV HGS 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 plus bevacizumab combination. (EB, B, S, H)
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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, B/H, S, I)

Note: As of this writing, veliparib is not commercially available.

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Recurrent Ovarian Cancer: Second-Line or Greater Maintenance and Treatment

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.
  • Options include: olaparib 300 mg every 12 hours; rucaparib 600 mg every 12 hours; niraparib 200-300 mg once daily.
(EB, B, S, H)
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Treatment with a PARPi should be offered to patients with recurrent EOC who have not already received a PARPi and have a germline or somatic pathogenic or likely pathogenic variants in BRCA1 or BRCA2 genes.
  • Options include: olaparib 300 mg every 12 hours; rucaparib 600 mg every 12 hours; niraparib 200-300 mg once daily.
(EB, B, S, H)
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Treatment with a PARPi monotherapy should be offered to patients with recurrent EOC who have not already received a PARPi and whose tumor demonstrates genomic instability, as determined by Myriad myChoice CDx, and has not recurred within 6 months of platinum-based therapy. (EB, B, S, H)
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PARPis are not recommended for treatment of BRCA wild-type or platinum-resistant recurrent EOC. (EB, B, S, H)
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PARPis in Combination

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, B, S, Ins)
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Management of Adverse Events

Anemia

  1. Patients requiring a blood transfusion for symptom relief and/or hemoglobin level < 8 g/dL should be monitored. PARPi dose should be reduced with evidence of repeated anemia to avoid multiple transfusions.
  2. 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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Neutropenia

  1. Growth factor is not indicated for use in patients receiving daily PARPi.
  2. 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.
(IC, B, M, Ins)
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Platelets

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

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

  1. Many patients will have tachyphylaxis of nausea symptoms over the first cycle of therapy.
  2. Persistent nausea requiring daily antiemetic intervention, causing a reduction in performance status, and/or resulting in > 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

August 13, 2020

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

Scope

Management, Treatment

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

DOI: 10.1200/JCO.20.01924 Journal of Clinical Oncology