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      PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline

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          Abstract

          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/s BRCA1) or BRCA2 (g/s BRCA2) genes should be treated with olaparib. The addition of olaparib to bevacizumab may be offered to patients with stage III-IV EOC with g/s BRCA1/2 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/s BRCA1/2, 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. Additional information is available at www.asco.org/gynecologic-cancer-guidelines .

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          Most cited references16

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          Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study.

          Olaparib (AZD2281) is a small-molecule, potent oral poly(ADP-ribose) polymerase (PARP) inhibitor. We aimed to assess the safety and tolerability of this drug in patients without BRCA1 or BRCA2 mutations with advanced triple-negative breast cancer or high-grade serous and/or undifferentiated ovarian cancer. In this phase 2, multicentre, open-label, non-randomised study, women with advanced high-grade serous and/or undifferentiated ovarian carcinoma or triple-negative breast cancer were enrolled and received olaparib 400 mg twice a day. Patients were stratified according to whether they had a BRCA1 or BRCA2 mutation or not. The primary endpoint was objective response rate by Response Evaluation Criteria In Solid Tumors (RECIST). All patients who received treatment were included in the analysis of toxic effects, and patients who had measurable lesions at baseline were included in the primary efficacy analysis. This trial is registered at ClinicalTrials.gov, number NCT00679783. 91 patients were enrolled (65 with ovarian cancer and 26 breast cancer) and 90 were treated between July 8, 2008, and Sept 24, 2009. In the ovarian cancer cohorts, 64 patients received treatment. 63 patients had target lesions and therefore were evaluable for objective response as per RECIST. In these patients, confirmed objective responses were seen in seven (41%; 95% CI 22-64) of 17 patients with BRCA1 or BRCA2 mutations and 11 (24%; 14-38) of 46 without mutations. No confirmed objective responses were reported in patients with breast cancer. The most common adverse events were fatigue (45 [70%] of patients with ovarian cancer, 13 [50%] of patients with breast cancer), nausea (42 [66%] and 16 [62%]), vomiting (25 [39%] and nine [35%]), and decreased appetite (23 [36%] and seven [27%]). Our study suggests that olaparib is a promising treatment for women with ovarian cancer and further assessment of the drug in clinical trials is needed. AstraZeneca. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas.

            Hallmarks of germline BRCA1/2-associated ovarian carcinomas include chemosensitivity and improved survival. The therapeutic impact of somatic BRCA1/2 mutations and mutations in other homologous recombination DNA repair genes is uncertain.
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              Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial

              Late-line treatment options for patients with ovarian cancer are few, with the proportion of patients achieving an overall response typically less than 10%, and median overall survival after third-line therapy of 5-9 months. In this study (QUADRA), we investigated the activity of niraparib monotherapy as the fourth or later line of therapy.
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                Author and article information

                Journal
                Journal of Clinical Oncology
                JCO
                American Society of Clinical Oncology (ASCO)
                0732-183X
                1527-7755
                August 13 2020
                : JCO.20.01924
                Affiliations
                [1 ]Memorial Sloan Kettering Cancer Center, New York, NY
                [2 ]American Society of Clinical Oncology, Alexandria, VA
                [3 ]SHARE Cancer Support, New York, NY
                [4 ]Ovarian Cancer Research Alliance, New York, NY
                [5 ]Ovarian Cancer Project, Williamsville, NY
                [6 ]The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom
                [7 ]Kaiser Permanente, San Francisco, CA
                [8 ]DeCesaris Cancer Institute, Anne Arundel Medical Center, Annapolis, MD
                [9 ]National Cancer Institute, Bethesda, MD
                [10 ]University Health Network, Toronto, Ontario, Canada
                [11 ]Dana-Farber Cancer Institute, Boston, MA
                [12 ]Stephenson Cancer Center, Oklahoma City, OK
                [13 ]University of New Mexico, Albuquerque, NM
                [14 ]Virginia Cancer Specialists, Arlington, VA
                [15 ]Cedars-Sinai, West Hollywood, CA
                [16 ]University of Texas MD Anderson Cancer Center, Houston, TX
                Article
                10.1200/JCO.20.01924
                32790492
                4f4f5408-d6b1-445b-ae25-a5104b460cb6
                © 2020
                History

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