Incorporating Parp-inhibitors in Primary and Recurrent Ovarian Cancer: A Meta-analysis of 12 phase II/III randomized controlled trials

Affiliations

¹ Gynecology Division, Department of Medical and Surgical Sciences and Translational Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Gynaecology, European Competence Center for Ovarian Cancer, Campus Virchow Clinic, 13353 Berlin, Germany; Laboratory of Tumor Immunology and Cell Therapy Unit, Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy. Electronic address: ilary.ruscito@uniroma1.it.
² Gynecology Division, Department of Medical and Surgical Sciences and Translational Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy.
³ Oncologie Médicale, Centre Leon Bérard, Univ Lyon, Université Claude Bernard Lyon1, Hesper EA 7425, F - 69003 Lyon, France.
⁴ Nordic Society of Gynaecological Oncology, Copenhagen, Denmark; Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
⁵ Department of Gynecology and Gynecologic Oncology, Evang. Kliniken Essen-Mitte, Henricistrasse 92, 45136 Essen, Germany.
⁶ Department of Obstetrics and Gynecology, Università della Svizzera Italiana, Lugano, Switzerland.
⁷ Laboratory of Tumor Immunology and Cell Therapy Unit, Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
⁸ Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy.
⁹ Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Stanford University School of Medicine, Stanford, CA, USA.
¹⁰ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Gynaecology, European Competence Center for Ovarian Cancer, Campus Virchow Clinic, 13353 Berlin, Germany.

PMID: 32485510
DOI: 10.1016/j.ctrv.2020.102040

Meta-Analysis

Incorporating Parp-inhibitors in Primary and Recurrent Ovarian Cancer: A Meta-analysis of 12 phase II/III randomized controlled trials

Ilary Ruscito et al. Cancer Treat Rev. 2020 Jul.

. 2020 Jul:87:102040.

doi: 10.1016/j.ctrv.2020.102040. Epub 2020 May 26.

Affiliations

¹ Gynecology Division, Department of Medical and Surgical Sciences and Translational Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Gynaecology, European Competence Center for Ovarian Cancer, Campus Virchow Clinic, 13353 Berlin, Germany; Laboratory of Tumor Immunology and Cell Therapy Unit, Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy. Electronic address: ilary.ruscito@uniroma1.it.
² Gynecology Division, Department of Medical and Surgical Sciences and Translational Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy.
³ Oncologie Médicale, Centre Leon Bérard, Univ Lyon, Université Claude Bernard Lyon1, Hesper EA 7425, F - 69003 Lyon, France.
⁴ Nordic Society of Gynaecological Oncology, Copenhagen, Denmark; Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
⁵ Department of Gynecology and Gynecologic Oncology, Evang. Kliniken Essen-Mitte, Henricistrasse 92, 45136 Essen, Germany.
⁶ Department of Obstetrics and Gynecology, Università della Svizzera Italiana, Lugano, Switzerland.
⁷ Laboratory of Tumor Immunology and Cell Therapy Unit, Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
⁸ Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy.
⁹ Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Stanford University School of Medicine, Stanford, CA, USA.
¹⁰ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Gynaecology, European Competence Center for Ovarian Cancer, Campus Virchow Clinic, 13353 Berlin, Germany.

PMID: 32485510
DOI: 10.1016/j.ctrv.2020.102040

Abstract

Background: The second decade of 2000s is witnessing a new ovarian cancer (OC) paradigm shift thanks to the results recently obtained by a new class of targeted agents: the Poly(ADP-ribose)polymerase (PARP)-Inhibitors (PARPi). Aim of this meta-analysis is to analyze available results obtained with PARPi, administered alone or in combination with chemo- and/or target-therapies in terms of efficacy and safety for the treatment of recurrent and primary advanced OC.

Methods: On December 2019, all published phase II/III randomized clinical studies were systematically searched using the terms "[Parp-Inhibitor] AND [ovar*]". Twelve phase II/III randomized controlled trials were identified, with a total number of 5171 patients included.

Results: Results demonstrated that PARPi account for a significant improvement of PFS in both recurrent and primary OC setting, independently from their administration schedule and independently from patients' BRCA mutational status. Moreover, patients harboring a Homologous Recombination Deficiency (HRD) positive testing primary or recurrent OC progress significantly later after PARPi administration/association. Results also reported that PARPi increase the occurrence of severe (G3-G4) anemia. Furthermore, severe fatigue occurred more frequently among patients subjected to PARPi combined with chemotherapy and to PARPi plus Bevacizumab. Finally, a significant increase in severe high blood pressure occurrence was observed when PARPi was added to antiangiogenetics, compared to PARPi alone but a significant decrease in G3-G4 hypertension occurrence was found in PARPi plus bevacizumab users compared to Bevacizumab alone.

Conclusions: PARPi are a valid option for the treatment of both primary and relapsed OC patients, with a relative low incidence of severe side effects.

Keywords: Niraparib; Olaparib; Ovarian cancer; Parp-inhibitor; Rucaparib; Veliparib.

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Incorporating Parp-inhibitors in Primary and Recurrent Ovarian Cancer: A Meta-analysis of 12 phase II/III randomized controlled trials

Affiliations

Incorporating Parp-inhibitors in Primary and Recurrent Ovarian Cancer: A Meta-analysis of 12 phase II/III randomized controlled trials

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Medical