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  1. Article ; Online: PARP inhibitor associated treatment related myeloid neoplasms: What was a "Rare" complication may be less so.

    Moore, Kathleen N

    Gynecologic oncology

    2021  Volume 161, Issue 3, Page(s) 639–641

    MeSH term(s) Antineoplastic Agents ; Humans ; Neoplasms, Second Primary ; Phthalazines ; Poly(ADP-ribose) Polymerase Inhibitors
    Chemical Substances Antineoplastic Agents ; Phthalazines ; Poly(ADP-ribose) Polymerase Inhibitors
    Language English
    Publishing date 2021-08-06
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 801461-9
    ISSN 1095-6859 ; 0090-8258
    ISSN (online) 1095-6859
    ISSN 0090-8258
    DOI 10.1016/j.ygyno.2021.05.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Testing for High-Risk Human Papillomavirus in Lower Genital Tract Tumors: If Knowledge Does Not Translate to an Action That Helps Patients-Why Do It?

    Moore, Kathleen N / Monk, Bradley J

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2022  Volume 40, Issue 14, Page(s) 1514–1517

    MeSH term(s) Alphapapillomavirus/genetics ; Genitalia ; Humans ; Neoplasms ; Papillomaviridae ; Papillomavirus Infections/complications ; Papillomavirus Infections/diagnosis
    Language English
    Publishing date 2022-03-30
    Publishing country United States
    Document type Editorial ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.22.00251
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Resistance to Poly (ADP-Ribose) Polymerase Inhibitors (PARPi): Mechanisms and Potential to Reverse.

    Washington, Christina R / Moore, Kathleen N

    Current oncology reports

    2022  Volume 24, Issue 12, Page(s) 1685–1693

    Abstract: Purpose of review: This review will focus on the most common mechanisms for poly (ADP-ribose) polymerase inhibitors' (PARPi) resistance and the main strategies for overcoming acquired or de novo PARPi resistance.: Recent findings: Initial approvals ... ...

    Abstract Purpose of review: This review will focus on the most common mechanisms for poly (ADP-ribose) polymerase inhibitors' (PARPi) resistance and the main strategies for overcoming acquired or de novo PARPi resistance.
    Recent findings: Initial approvals for PARPi as part of treatment for advanced epithelial ovarian cancer (EOC) started in 2014 with patient with recurrent cancer characterized by BRCA mutations in the 3rd and 4th line and now have approvals for front-line maintenance in both the BRCA mutated and BRCAwt populations. As with all therapies, patients will eventually develop resistance to treatment. The most common mechanisms for PARPi resistance include reversion mutations, methylation events, and restoration of homologous recombination deficiency (HRD) through combinations and targeting replication stress. As more and more patients receive initial treatment (and potential retreatment with PARPi), we need to better understand the mechanisms in which tumors acquire PARPi resistance.
    MeSH term(s) Female ; Humans ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Ribose/therapeutic use ; Neoplasm Recurrence, Local/drug therapy ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Adenosine Diphosphate/therapeutic use
    Chemical Substances Poly(ADP-ribose) Polymerase Inhibitors ; Ribose (681HV46001) ; Adenosine Diphosphate (61D2G4IYVH)
    Language English
    Publishing date 2022-11-08
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2057359-5
    ISSN 1534-6269 ; 1523-3790
    ISSN (online) 1534-6269
    ISSN 1523-3790
    DOI 10.1007/s11912-022-01337-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Poly(ADP-Ribose) Polymerase Inhibitor Inhibition in Ovarian Cancer: A Comprehensive Review.

    Moore, Kathleen N / Pothuri, Bhavana

    Cancer journal (Sudbury, Mass.)

    2021  Volume 27, Issue 6, Page(s) 432–440

    Abstract: Abstract: The emergence of clinical trial data for poly(ADP-ribose) polymerase inhibitors (PARPi), in BRCA-associated ovarian cancer (epithelial ovarian cancer [EOC]) in 2009 (Lancet 2010;376:245-251) unleashed a rapid series of additional asset ... ...

    Abstract Abstract: The emergence of clinical trial data for poly(ADP-ribose) polymerase inhibitors (PARPi), in BRCA-associated ovarian cancer (epithelial ovarian cancer [EOC]) in 2009 (Lancet 2010;376:245-251) unleashed a rapid series of additional asset development and clinical trial activation across all lines of EOC treatment, ultimately leading to 8 new approvals of 3 different PARPi in EOC since 2014. Monotherapy iPARPi were approved as frontline maintenance treatment for all patients with EOC who respond to platinum-based chemotherapy irrespective of biomarker (niraparib) and for BRCA-associated cancers (olaparib) (https://www.azpicentral.com/lynparza_tb/lynparza_tb.pdf#page=1; https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208447s015s017lbledt.pdf). Combination of olaparib and bevacizumab was approved as maintenance for patients in response to platinum-based and bevacizumab containing frontline therapy whose tumor is characterized as homologous recombination deficient and as approved test by the Food and Drug Administration, inclusive of BRCA-associated cancers (N Engl J Med 2019;381:2416-2428). Niraparib, olaparib, and rucaparib were also approved as maintenance treatment following response to platinum-based therapy in the recurrent setting irrespective of biomarker (https://www.azpicentral.com/lynparza_tb/lynparza_tb.pdf#page=1; https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208447s015s017lbledt.pdf; https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209115s003lbl.pdf). All 3 PARPi were also approved as treatment in lieu of chemotherapy for patients with BRCA-associated cancers in third line and beyond (https://www.azpicentral.com/lynparza_tb/lynparza_tb.pdf#page=1;https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209115s003lbl.pdf) and platinum-sensitive homologous recombination deficient in the fourth line and beyond (https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208447s015s017lbledt.pdf), as well as the National Comprehensive Cancer Network listed in combination with bevacizumab for treatment of patients with platinum-sensitive recurrent disease (https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf). Ongoing clinical trials in all lines of treatment are evaluating combinations of therapies to improve efficacy among biomarker negative tumors as well as overcome acquired PARPi resistance due to prior use.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Carcinoma, Ovarian Epithelial/drug therapy ; Carcinoma, Ovarian Epithelial/genetics ; Humans ; Neoplasm Recurrence, Local ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use
    Chemical Substances Antineoplastic Agents ; Poly(ADP-ribose) Polymerase Inhibitors
    Language English
    Publishing date 2021-12-14
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2018400-1
    ISSN 1540-336X ; 1528-9117 ; 1081-4442
    ISSN (online) 1540-336X
    ISSN 1528-9117 ; 1081-4442
    DOI 10.1097/PPO.0000000000000558
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: PARP inhibitors in the treatment of ovarian cancer: a review.

    Washington, Christina R / Moore, Kathleen N

    Current opinion in obstetrics & gynecology

    2020  Volume 33, Issue 1, Page(s) 1–6

    Abstract: Purpose of review: This article will review recent changes in the standard of care for olaparib, niraparib, and rucaparib, as well as ongoing trials evaluating this class of drugs in combination with antiangiogenic agents and PD-1/PD-L1 inhibitors.: ... ...

    Abstract Purpose of review: This article will review recent changes in the standard of care for olaparib, niraparib, and rucaparib, as well as ongoing trials evaluating this class of drugs in combination with antiangiogenic agents and PD-1/PD-L1 inhibitors.
    Recent findings: Niraparib received FDA approval for use in patients with complete response or partial response to first-line platinum-based chemotherapy regardless of BRCAm or HRD status that was received in April 2020. FDA approval was received for olaparib in combination with bevacizamab for epithelial ovarian cancer patients with complete response/partial response to first-line chemotherapy and bevacizumab and g/sBRCA and/or genomic instability by Myriad myChoice CDx in May 2020.
    Summary: In the last year, treatment with PARPi has extended to not only include BRCAm and HRD-deficient patients but also have shown improvement in outcomes in HRD-proficient patients. With these advancements, more patients can access these agents and receive benefit. In the upcoming years, it will be exciting to see the potential benefit when PARPs are added to other angiogenic antagonists and immunotherapy agents.
    MeSH term(s) Carcinoma, Ovarian Epithelial/drug therapy ; Female ; Humans ; Ovarian Neoplasms/drug therapy ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use
    Chemical Substances Poly(ADP-ribose) Polymerase Inhibitors
    Language English
    Publishing date 2020-12-22
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1049382-7
    ISSN 1473-656X ; 1040-872X
    ISSN (online) 1473-656X
    ISSN 1040-872X
    DOI 10.1097/GCO.0000000000000675
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Germline and Somatic Testing in Ovarian Cancer: Shifting Sands of Recommendations.

    Moore, Kathleen N / Zorn, Kristin K

    Gynecologic oncology

    2020  Volume 156, Issue 3, Page(s) 515–516

    MeSH term(s) Carcinoma, Ovarian Epithelial/genetics ; Carcinoma, Ovarian Epithelial/pathology ; Female ; Genetic Testing/methods ; Germ-Line Mutation ; Humans ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology
    Language English
    Publishing date 2020-02-24
    Publishing country United States
    Document type Editorial
    ZDB-ID 801461-9
    ISSN 1095-6859 ; 0090-8258
    ISSN (online) 1095-6859
    ISSN 0090-8258
    DOI 10.1016/j.ygyno.2020.02.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: PARP Inhibitors in Ovarian Cancer: A Review.

    O'Malley, David M / Krivak, Thomas C / Kabil, Nashwa / Munley, Jiefen / Moore, Kathleen N

    Targeted oncology

    2023  Volume 18, Issue 4, Page(s) 471–503

    Abstract: Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have transformed the ovarian cancer (OC) treatment landscape. This narrative review provides a comprehensive overview of data for the PARPis olaparib, niraparib, and rucaparib in patients with OC and ...

    Abstract Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have transformed the ovarian cancer (OC) treatment landscape. This narrative review provides a comprehensive overview of data for the PARPis olaparib, niraparib, and rucaparib in patients with OC and discusses their role in disease management, with a focus on the use of PARPis as maintenance therapy in the United States (US). Olaparib was the first PARPi to be approved as first-line maintenance monotherapy in the US, with maintenance niraparib subsequently approved in the first-line setting. Data also support the efficacy of rucaparib as first-line maintenance monotherapy. PARPi maintenance combination therapy (olaparib plus bevacizumab) also provides benefit in patients with newly diagnosed advanced OC whose tumors tested positive for homologous recombination deficiency (HRD). Biomarker testing is critical in the newly diagnosed setting to identify patients most likely to benefit from PARPi maintenance therapy and guide treatment decisions. Clinical trial data support the use of PARPis (olaparib, niraparib, rucaparib) as second-line or later maintenance therapy in patients with platinum-sensitive relapsed OC. Although distinct differences in tolerability profile were observed between PARPis, they were generally well tolerated, with the majority of adverse events managed by dose modification. PARPis had no detrimental effect on patients' health-related quality of life. Real-world data support the use of PARPis in OC, although some differences between PARPis are apparent. Data from trials investigating novel combination strategies, such as PARPis plus immune checkpoint inhibitors, are awaited with interest; the optimal sequencing of novel therapies in OC remains to be established.
    MeSH term(s) Humans ; Female ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Quality of Life ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/pathology ; Carcinoma, Ovarian Epithelial/drug therapy ; Bevacizumab/therapeutic use
    Chemical Substances Poly(ADP-ribose) Polymerase Inhibitors ; Bevacizumab (2S9ZZM9Q9V)
    Language English
    Publishing date 2023-06-03
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 2222136-0
    ISSN 1776-260X ; 1776-2596
    ISSN (online) 1776-260X
    ISSN 1776-2596
    DOI 10.1007/s11523-023-00970-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Trials in progress: IMagyn050/GOG 3015/ENGOT-OV39. A Phase III, multicenter, randomized study of atezolizumab versus placebo administered in combination with paclitaxel, carboplatin, and bevacizumab to patients with newly-diagnosed stage III or stage IV ovarian, fallopian tube, or primary peritoneal cancer.

    Moore, Kathleen N / Pignata, Sandro

    International journal of gynecological cancer : official journal of the International Gynecological Cancer Society

    2019  

    Abstract: Background: There is mounting pre-clinical and clinical evidence that combinations of immunotherapy, specifically programed cell death-1 (PD-1) inhibition, with chemotherapy and anti-angiogenesis agents, such as bevacizumab, result in markedly improved ... ...

    Abstract Background: There is mounting pre-clinical and clinical evidence that combinations of immunotherapy, specifically programed cell death-1 (PD-1) inhibition, with chemotherapy and anti-angiogenesis agents, such as bevacizumab, result in markedly improved outcomes across a variety of tumor types including endometrial cancer, renal cell cancer, and non-small cell lung cancer. IMagyn050/GOG 3015/ENGOT-OV39 is the first, randomized, phase III trial to evaluate the potential impact of this combination on both progression-free survival and overall survival in patients presenting with advanced epithelial ovarian cancer.
    Primary objective: The primary objective is to evaluate the efficacy of atezolizumab versus placebo in combination with paclitaxel + carboplatin + bevacizumab for front-line treatment of ovarian cancer among all patients and those with PD-L1+ tumors.
    Study hypothesis: This study will test the hypothesis that treatment with atezolizumab added to paclitaxel, carboplatin, and bevacizumab will prolong progression-free survival and overall survival compared with treatment with placebo plus paclitaxel, carboplatin, and bevacizumab.
    Trial design: This is a randomized, phase III, placebo-controlled study.
    Major inclusion/exclusion criteria: Eligible patients have a histologic diagnosis of advanced epithelial ovarain cancer, primary peritoneal, or fallopian tube cancer who either have residual disease after primary surgery or who are undergoing neoadjuvant chemotherapy with planned interval surgery. Ineligible patients include those who are cured with surgery alone or those for whom no gross residual disease remained following primary cytoreduction.
    Primary endpoint: There are two co-primary efficacy endpoints: investigator-assessed progression-free survival and overall survival.
    Sample size: 1300 patients.
    Estimated dates for completing accrual and presenting results: April 2020.
    Trial registration: NCT03038100.
    Language English
    Publishing date 2019-01-10
    Publishing country England
    Document type Journal Article
    ZDB-ID 1070385-8
    ISSN 1525-1438 ; 1048-891X
    ISSN (online) 1525-1438
    ISSN 1048-891X
    DOI 10.1136/ijgc-2018-000071
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Administration of the Tablet Formulation of Olaparib in Patients with Ovarian Cancer: Practical Guidance and Expectations.

    Moore, Kathleen N / Birrer, Michael J

    The oncologist

    2018  Volume 23, Issue 6, Page(s) 697–703

    Abstract: Olaparib is a poly(ADP-ribose) polymerase enzyme inhibitor that is approved for use in patients with advanced ovarian cancer (OC) and genetic : Implications for practice: Olaparib has recently been approved for maintenance treatment of recurrent ... ...

    Abstract Olaparib is a poly(ADP-ribose) polymerase enzyme inhibitor that is approved for use in patients with advanced ovarian cancer (OC) and genetic
    Implications for practice: Olaparib has recently been approved for maintenance treatment of recurrent ovarian cancer (OC) that is in response to platinum-based chemotherapy. The originally approved capsule formulation was dosed as 400 mg twice daily (eight 50 mg capsules). The recommended olaparib tablet dose is 300 mg twice daily (two 150 mg tablets). The tablet is the new approved formulation based on the SOLO-2 trial results. Because the capsule and tablet formulations have different bioavailability, physicians must strictly adhere to the dosing instructions provided in the prescribing information. The tablet offers greater convenience for most patients, especially when using olaparib for maintenance therapy. This review discusses the differences between the two formulations, dose determination, and guidance for use of olaparib tablets by patients with OC.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Female ; Humans ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/pathology ; Phthalazines/pharmacology ; Phthalazines/therapeutic use ; Piperazines/pharmacology ; Piperazines/therapeutic use ; Tablets/pharmacology ; Tablets/therapeutic use
    Chemical Substances Antineoplastic Agents ; Phthalazines ; Piperazines ; Tablets ; olaparib (WOH1JD9AR8)
    Language English
    Publishing date 2018-03-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1409038-7
    ISSN 1549-490X ; 1083-7159
    ISSN (online) 1549-490X
    ISSN 1083-7159
    DOI 10.1634/theoncologist.2017-0485
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Niraparib for the treatment of ovarian cancer.

    Essel, Kathleen G / Moore, Kathleen N

    Expert review of anticancer therapy

    2018  Volume 18, Issue 8, Page(s) 727–733

    Abstract: Introduction: Niraparib, an orally available selective inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP), is the first PARP inhibitor approved for use in patients with ovarian cancer who do not harbor a germ-line or somatic mutation in ... ...

    Abstract Introduction: Niraparib, an orally available selective inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP), is the first PARP inhibitor approved for use in patients with ovarian cancer who do not harbor a germ-line or somatic mutation in the breast cancer gene (BRCA). Overall, niraparib is well tolerated and its toxicities, primarily hematologic, are manageable especially with recently released initial dose modification guidelines based on weight and baseline platelet count. The role of niraparib as maintenance following frontline platinum-based chemotherapy as well as in the treatment of recurrent high-grade serous ovarian cancer is an active area of investigation. Areas covered: This review focuses on niraparib, its pharmacology, clinical efficacy, and adverse effects as evidenced by prospective clinical trials, and licensed indications. Expert commentary: Niraparib introduced the use of PARP inhibitors regardless of biomarker status. Recent studies highlight the critical need for more accurate biomarkers to identify patients most likely to benefit from treatment with PARP inhibitors. In the next 5 years, we anticipate further expansion of and elucidation regarding the optimal indication for use of niraparib in the treatment of ovarian cancer.
    MeSH term(s) Biomarkers, Tumor/metabolism ; Dose-Response Relationship, Drug ; Female ; Humans ; Indazoles/administration & dosage ; Indazoles/adverse effects ; Indazoles/pharmacology ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Piperidines/administration & dosage ; Piperidines/adverse effects ; Piperidines/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage ; Poly(ADP-ribose) Polymerase Inhibitors/adverse effects ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Practice Guidelines as Topic
    Chemical Substances Biomarkers, Tumor ; Indazoles ; Piperidines ; Poly(ADP-ribose) Polymerase Inhibitors ; niraparib (HMC2H89N35)
    Language English
    Publishing date 2018-07-02
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2112544-2
    ISSN 1744-8328 ; 1473-7140
    ISSN (online) 1744-8328
    ISSN 1473-7140
    DOI 10.1080/14737140.2018.1490180
    Database MEDical Literature Analysis and Retrieval System OnLINE

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