INOVATYON/ ENGOT-ov5 study: Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line
British Journal of Cancer, vol. 128, pp. 1503–1513
Abstract
BACKGROUND: This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC). METHODS: Patients with OC (up to two previous platinum-based lines), with a TFIp of 6-12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75). RESULTS: The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94-1.35; p = 0.197). Grade 3-5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP). CONCLUSIONS: This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6-12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT01379989.
Authors 67
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European Institute of Oncology
Affiliation as printed
Gynecologic Cancer Program, European Institute of Oncology IRCCS and University of Milan-Bicocca, Milan, Italy
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Affiliation as printed
Clinical and Experimental Medicine, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy
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Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie · Charité - Universitätsmedizin Berlin
Affiliation as printed
North Eastern German Society of Gynecological Oncology (NOGGO) Study group and Gynecology with Center for Oncological Surgery, European Competence Center for Ovarian Cancer, Charité-Berlin University of Medicine, Berlin, Germany
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Mario Negri Institute for Pharmacological Research
Affiliation as printed
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
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Tampere University · Tampere University Hospital
Affiliation as printed
Nordic Society of Gynecologic Oncology Clinical Trial Unit (NSGO-CTU) & Department of Obstetrics and Gynaecology and Tays Cancer Centre Tampere University and University Hospital, Tampere, Finland
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Swiss Group For Clinical Cancer Research · Istituto Oncologico della Svizzera Italiana
Affiliation as printed
Istituto Oncologico della Svizzera Italiana, IOSI and Swiss Group for Clinical Cancer Research (SAKK), Bellinzona, Switzerland
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Radboud University Medical Center
Affiliation as printed
Medical Oncology, Radboud University Medical Center, Nijmegen, Netherlands
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Innsbruck Medical University · Universität Innsbruck · AGO Austria
Affiliation as printed
Medical University of Innsbruck, Department for Gynecology and Obstetrics, Innsbruck, Austria, and AGO, Innsbruck, Austria
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Affiliation as printed
Gynecologic Oncology, University Hospitals Leuven, Leuven Cancer Institute, and Belgian Gynaecological Oncology Group (BGOG), European Union, Leuven, Belgium
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Humanitas University · Mario Negri Institute for Pharmacological Research
Affiliation as printed
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
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Spanish Ovarian Cancer Research Group
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Hospital de Donosti San Sebastián and Grupo Español de Cáncer de Ovario (GEICO), de Donosti San, Spain
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Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie · Charité - Universitätsmedizin Berlin
Affiliation as printed
North Eastern German Society of Gynecological Oncology (NOGGO) Study group and Gynecology with Center for Oncological Surgery, European Competence Center for Ovarian Cancer, Charité-Berlin University of Medicine, Berlin, Germany
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Odense University Hospital · Nordic Society of Gynecologic Oncology
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Nordic Society of Gynecologic Oncology Clinical Trial Unit (NSGO-CTU) & Department of Oncology, Odense University Hospital, Odense, Denmark
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Kantonsspital St. Gallen · Swiss Group For Clinical Cancer Research
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Oncology, Kantonsspital St. Gallen and Swiss Group for Clinical Cancer Research (SAKK), St. Gallen, Switzerland
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Brighton and Sussex University Hospitals NHS Trust
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Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
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Mario Negri Institute for Pharmacological Research
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Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
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Institut Català d'Oncologia · Spanish Ovarian Cancer Research Group
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Institut Catalá de Oncología de Girona and Grupo Español de Cáncer de Ovario (GEICO), de Donosti San, Spain
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Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie
Affiliation as printed
North Eastern German Society of Gynecological Oncology (NOGGO) Study group and CaritasKlinikum St. Theresia-Saarbruecken, Saarbruecken, Germany
North Eastern German Society of Gynecological Oncology (NOGGO) Study group and CaritasKlinikum St. Theresia—Saarbruecken, Saarbruecken, Germany
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Copenhagen University Hospital · Nordic Society of Gynecologic Oncology
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Nordic Society of Gynecologic Oncology Clinical Trial Unit (NSGO-CTU) & Department of Cancer Treatment, Copenhagen University Hospital, Copenhagen, Denmark
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Mario Negri Institute for Pharmacological Research
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Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy. elena.biagioli@marionegri.it
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
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Mario Negri Institute for Pharmacological Research · Hospital Son Llatzer · Spanish Ovarian Cancer Research Group
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Hospital Son Llázter and Grupo Español de Cáncer de Ovario (GEICO), Palma, Spain
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
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Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia · Spanish Ovarian Cancer Research Group · University of Brescia
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Obstetrics and Gynaecology, ASST Spedali Civili-Università degli Studi di Brescia, Brescia, Italy
Hospital Reina Sofía Córdoba and Grupo Español de Cáncer de Ovario (GEICO), de Donosti San, Spain
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Ente Ospedaliero Ospedali Galliera · Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
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S.C. Oncologia Medica, E.O. Ospedali Galliera, Genoa, Italy
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
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Policlinico Umberto I · Candiolo Cancer Institute · University of Turin
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AOU Policlinico Umberto I di Roma, Rome, Italy
Istituto di Candiolo, FPO-IRCCS and University of Torino, Torino, Italy
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Innsbruck Medical University · Universität Innsbruck · AGO Austria · Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie · Technische Universität Dresden
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Medical University of Innsbruck, Department for Gynecology and Obstetrics, Innsbruck, Austria, and AGO, Innsbruck, Austria
North Eastern German Society of Gynecological Oncology (NOGGO) Study group and Department of Gynecology and Obstetrics, Technische Universität Dresden, Fetscherstr, Dresden, Germany
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Mario Negri Institute for Pharmacological Research · Istituto Oncologico Veneto
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Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
Oncologia 2, Istituto Oncologico Veneto, Padua, Italy
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Mario Negri Institute for Pharmacological Research · Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia · University of Brescia
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Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
Obstetrics and Gynaecology, ASST Spedali Civili-Università degli Studi di Brescia, Brescia, Italy
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Mario Negri Institute for Pharmacological Research · Ente Ospedaliero Ospedali Galliera
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Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
S.C. Oncologia Medica, E.O. Ospedali Galliera, Genoa, Italy
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Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori · Istituto Oncologico Veneto
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Oncologia 2, Istituto Oncologico Veneto, Padua, Italy
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
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Azienda Ospedaliera Citta' della Salute e della Scienza di Torino · Istituto Oncologico Veneto
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Oncologia 2, Istituto Oncologico Veneto, Padua, Italy
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Azienda Ospedaliera Citta' della Salute e della Scienza di Torino · Ospedale Infermi di Rimini
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Policlinico Umberto I · IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola
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Policlinico Umberto I · Azienda Sanitaria Unità Locale di Reggio Emilia
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Ospedale Policlinico San Martino · Fondazione Poliambulanza Istituto Ospedaliero
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Azienda Ospedaliero Universitaria Maggiore della Carita · Ospedale Policlinico San Martino
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Ospedale Filippo Del Ponte Varese · Azienda Ospedaliero Universitaria Maggiore della Carita
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Policlinico Umberto I · Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo · Sapienza University of Rome
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Azienda Ospedaliera S. Croce e Carle, Cuneo, Italy
Policlinico Umberto I, Università di Roma "La Sapienza", Roma, Italy
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Fondazione Poliambulanza Istituto Ospedaliero · Ospedale di Prato Santo Stefano
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Azienda Ospedaliero Universitaria Maggiore della Carita · Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo
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Ospedale degli Infermi · Azienda Ospedaliero Universitaria Maggiore della Carita
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Policlinico Umberto I · Sapienza University of Rome
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Ospedale SS Trinità, Sora, Italy
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Ospedale degli Infermi · Policlinico San Matteo Fondazione
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Ospedale Degli Infermi, Biella, Italy
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A. O. Ordine Mauriziano di Torino
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Ospedale SS Trinità, Sora, Italy
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Guglielmo da Saliceto Hospital
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Azienda Ospedaliero-Universitaria di Modena · Policlinico San Matteo Fondazione
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Ospedale per gli Infermi · Policlinico San Matteo Fondazione
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A. O. Ordine Mauriziano di Torino
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Ospedale di Mirano · Guglielmo da Saliceto Hospital
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Azienda Ospedaliero-Universitaria di Modena · Alessandro Manzoni Hospital
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Ospedale Santa Chiara · Ospedale per gli Infermi
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Ospedale di Mirano · Ospedale Valduce
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Centro di Riferimento Oncologico della Basilicata · Alessandro Manzoni Hospital
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AO della Provincia di Lecco, Ospedale Alessandro Manzoni, Lecco, Italy
Istituto di Ricovero e Cura a Carattere Scientifico—Centro Regionale Oncologico Basilicata, Rionero in Vulture, Italy
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Ospedale Santa Chiara · Ospedale A. Perrino
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Ospedale di Santa Chiara, Trento, Italy
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Ospedale Regionale Umberto Parini, Aosta, Italy
ASL VC Ospedale S. Andrea, Vercelli, Italy
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Ospedale Sacro Cuore Don Calabria · Ospedale Valduce
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Ospedale Valduce, Como, Italy
Sacro Cuore Don Calabria, Negrar, Italy
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Centro di Riferimento Oncologico della Basilicata
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Istituto di Ricovero e Cura a Carattere Scientifico—Centro Regionale Oncologico Basilicata, Rionero in Vulture, Italy
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ARNAS Civico, Palermo, Italy
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ASL VC Ospedale S. Andrea, Vercelli, Italy
ARNAS Civico, Palermo, Italy
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Ospedale Sacro Cuore Don Calabria · University of Naples Federico II
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Sacro Cuore Don Calabria, Negrar, Italy
Università degli Studi di Napoli Federico II, Napoli, Italy
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Ospedale S. Vincenzo, Taormina, Italy
Ospedale San Giuseppe - Azienda, USL11, Empoli, Italy
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Spanish Ovarian Cancer Research Group
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ARNAS Civico, Palermo, Italy
Hospital de Donosti San Sebastián and Grupo Español de Cáncer de Ovario (GEICO), de Donosti San, Spain
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Institut Català d'Oncologia · Spanish Ovarian Cancer Research Group
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ARNAS Civico, Palermo, Italy
Institut Catalá de Oncología de Girona and Grupo Español de Cáncer de Ovario (GEICO), de Donosti San, Spain