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.

P Benedetti Panici, M Iglesias, G Funari, M Romeo, G Tasca, B Pardo, G Tognon, M J Rubio-Pérez, A DeCensi, U De Giorgi, P Zola, E Biagioli, M Aglietta, V Arcangeli, C Zamagni, A Bologna, A Westermann, V Heinzelmann-Schwarz, I Tsibulak, P Wimberger, A Poveda, M D'Incalci, A Gadducci, J Sehouli, E Rulli, J Mäenpää, C Sessa, A Montes, N B Ottevanger, R Berger, I Vergote, N Colombo, C Churruca Galaz, R Chekerov, G B Nyvang, S Riniker, R Herbertson, R Fossati, M P Barretina-Ginesta, M Deryal, M R Mirza

Journal: British journal of cancer 2023;128(8):1503-1513

PMID: 36759720

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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.

Address: Gynecologic Cancer Program, European Institute of Oncology IRCCS and University of Milan-Bicocca, Milan, Italy.; Clinical and Experimental Medicine, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy.; 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.; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.; 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.; Istituto Oncologico della Svizzera Italiana, IOSI and Swiss Group for Clinical Cancer Research (SAKK), Bellinzona, Switzerland.; Guys and St Thomas' NHS Foundation Trust, London, UK.; Medical Oncology, Radboud University Medical Center, Nijmegen, Netherlands.; Medical University of Innsbruck, Department for Gynecology and Obstetrics, Innsbruck, Austria, and AGO, Innsbruck, Austria.; Gynecologic Oncology, University Hospitals Leuven, Leuven Cancer Institute, and Belgian Gynaecological Oncology Group (BGOG), European Union, Leuven, Belgium.; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.; Hospital de Donosti San Sebastián and Grupo Español de Cáncer de Ovario (GEICO), de Donosti San, Spain.; Nordic Society of Gynecologic Oncology Clinical Trial Unit (NSGO-CTU) & Department of Oncology, Odense University Hospital, Odense, Denmark.; Oncology, Kantonsspital St. Gallen and Swiss Group for Clinical Cancer Research (SAKK), St. Gallen, Switzerland.; Brighton and Sussex University Hospitals NHS Trust, Brighton, UK.; Institut Catalá de Oncología de Girona and Grupo Español de Cáncer de Ovario (GEICO), de Donosti San, Spain.; North Eastern German Society of Gynecological Oncology (NOGGO) Study group and CaritasKlinikum St. Theresia-Saarbruecken, Saarbruecken, Germany.; Nordic Society of Gynecologic Oncology Clinical Trial Unit (NSGO-CTU) & Department of Cancer Treatment, Copenhagen University Hospital, Copenhagen, Denmark.; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy. [email protected].; Hospital Son Llázter and Grupo Español de Cáncer de Ovario (GEICO), Palma, Spain.; Institut Catalá de Oncología de Badalona and Grupo Español de Cáncer de Ovario (GEICO), de Donosti San, Spain.; Oncologia 2, Istituto Oncologico Veneto, Padua, Italy.; Institut Catalá de Oncología de Hospitalet and Grupo Español de Cáncer de Ovario (GEICO), Barcelona, Spain.; 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.; S.C. Oncologia Medica, E.O. Ospedali Galliera, Genoa, Italy.; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.; AOU Città della Salute e della Scienza - OIRM S. Anna, Torino, Italy.; AOU Policlinico Umberto I di Roma, Rome, Italy.; Istituto di Candiolo, FPO-IRCCS and University of Torino, Torino, Italy.; Ospedale Infermi, Rimini, Italy.; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.; Azienda Unità Sanitaria Locale di Reggio Emilia IRCCS, Reggio Emilia, Italy.; Amsterdam UMC, Amsterdam, Netherlands.; Universitätsspital Basel, USB andSwiss Group for Clinical Cancer Research (SAKK), Basel, Switzerland.; North Eastern German Society of Gynecological Oncology (NOGGO) Study group and Department of Gynecology and Obstetrics, Technische Universität Dresden, Fetscherstr, Dresden, Germany.; National Center for Tumor Diseases (NCT/UCC), Dresden, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany.; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany.; Initia Oncologia and Grupo Español de Cáncer de Ovario (GEICO), Valencia, Spain.

DOI: 10.1038/s41416-022-02108-7

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MeSH Terms: Humans, Female, Carboplatin, Trabectedin, Ovarian Neoplasms, Platinum, Neoplasm Recurrence, Local, Carcinoma, Ovarian Epithelial, Doxorubicin, Polyethylene Glycols, Antineoplastic Combined Chemotherapy Protocols