PARP Inhibitors in the Management of Ovarian Cancer
Guideline Status: Current
Published Online: August 25, 2022
Last Updated: April 20, 2023
Rapid Recommendation Update
Published online August 25, 2022.
Updated Recommendations:
Newly Diagnosed Ovarian Cancer
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.
Recurrent Ovarian Cancer: Second-Line or Greater Maintenance and Treatment
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. Options include: olaparib 300 mg every 12 hours, rucaparib 600 mg every 12 hours or niraparib 200-300 mg once daily
Maintenance treatment with niraparib for patients without germline or somatic BRCA mutation should weigh potential PFS benefit against possible overall survival decrement.
Recommendations 3.1/3.2 PARPi monotherapy should not be routinely offered to patients for the treatment of recurrent platinum sensitive EOC.
Evidence on PAPRi 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.
Recommendation 3.3 PARPi monotherapy is not recommended for treatment for patients with either BRCA wild-type or platinum-resistant recurrent EOC.
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).
Published ahead of print August 13, 2020, DOI: 10.1200/JCO.20.01924
William P. Tew, MD; Christina Lacchetti, MHSc; Annie Ellis; Kathleen Maxian, BSW; Susana Banerjee, PhD; Michael Bookman, MD; Monica Brown Jones, MD; Jung-Min Lee, MD; St´ephanie Lheureux, MD, PhD; Joyce F. Liu, MD; Kathleen N. Moore, MD; Carolyn Muller, MD; Patricia Rodriguez, MD; Christine Walsh, MD; Shannon N. Westin, MD; and Elise C. Kohn, MD
Purpose
To provide recommendations on the use of poly(ADP-ribose) polymerase inhibitors (PARPis) for management of epithelial ovarian, tubal, or primary peritoneal cancer (EOC).
Methods
Randomized, controlled, and open-labeled trials published from 2011 through 2020 were identified in a literature search. Guideline recommendations were based on the review of the evidence, US Food and Drug Administration approvals, and consensus when evidence was lacking.
Results
The systematic review identified 17 eligible trials.
Recommendations
The guideline pertains to patients who are PARPi naïve. All patients with newly diagnosed, stage III-IV EOC whose disease is in complete or partial response to first-line, platinum-based chemotherapy with high-grade serous or endometrioid EOC should be offered PARPi maintenance therapy with niraparib. For patients with germline or somatic pathogenic or likely pathogenic variants in BRCA1 (g/sBRCA1) or BRCA2 (g/sBRCA2) genes should be treated with olaparib. The addition of olaparib to bevacizumab may be offered to patients with stage III-IV EOC with g/sBRCA1/2 and/or genomic instability and a partial or complete response to chemotherapy plus bevacizumab combination. Maintenance therapy (second line or more) with single agent PARPi may be offered for patients with EOC who have not received a PARPi and have responded to platinum-based therapy regardless of BRCA mutation status. Treatment with a PARPi should be offered to patients with recurrent EOC that has not recurred within 6 months of platinum-based therapy, who have not received a PARPi and have a g/sBRCA1/2, or whose tumor demonstrates genomic instability. PARPis 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. Recommendations for managing specific adverse events are presented. Data to support reuse of PARPis in any setting are needed.
© 2020 American Society of Clinical Oncology, all rights reserved. For licensing opportunities, contact licensing@asco.org.
Guideline Disclaimer
The clinical practice guidelines and other guidance published herein are provided by the American Society of Clinical Oncology, Inc. ("ASCO") to assist practitioners in clinical decision making. The information therein should not be relied upon as being complete or accurate, nor should it be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. With the rapid development of scientific knowledge, new evidence may emerge between the time information is developed and when it is published or read. The information is not continually updated and may not reflect the most recent evidence. The information addresses only the topics specifically identified therein and is not applicable to other interventions, diseases, or stages of diseases. This information does not mandate any particular course of medical care. Further, the information is not intended to substitute for the independent professional judgment of the treating physician, as the information does not account for individual variation among patients. Recommendations reflect high, moderate or low confidence that the recommendation reflects the net effect of a given course of action. The use of words like "must," "must not," "should," and "should not" indicate that a course of action is recommended or not recommended for either most or many patients, but there is latitude for the treating physician to select other courses of action in individual cases. In all cases, the selected course of action should be considered by the treating physician in the context of treating the individual patient. Use of the information is voluntary. ASCO provides this information on an "as is" basis, and makes no warranty, express or implied, regarding the information. ASCO specifically disclaims any warranties of merchantability or fitness for a particular use or purpose. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of this information or for any errors or omissions.