Ilary Ruscito1, Filippo Bellati2, Isabelle Ray-Coquard3, Mansoor Raza Mirza4, Andreas du Bois5, Maria Luisa Gasparri6, Flavia Costanzi2, Maria Paola De Marco2, Marianna Nuti7, Donatella Caserta2, Sandro Pignata8, Oliver Dorigo9, Jalid Sehouli10, Elena Ioana Braicu10. 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.
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.
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.
Authors: E Krasniqi; A Sacconi; G Blandino; P Vici; D Marinelli; L Pizzuti; M Mazzotta; D Sergi; E Capomolla; S Donzelli; M Carosi; A Bagnato; T Gamucci; S Tomao; C Natoli; P Marchetti; A Grassadonia; N Tinari; M De Tursi; E Vizza; G Ciliberto; L Landi; F Cappuzzo; M Barba Journal: Biomark Res Date: 2021-07-13