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
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Published:2023-02-09
Issue:8
Volume:128
Page:1503-1513
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ISSN:0007-0920
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Container-title:British Journal of Cancer
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language:en
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Short-container-title:Br J Cancer
Author:
Colombo N., Gadducci A., Sehouli J., Rulli E., Mäenpää J., Sessa C., Montes A., Ottevanger N. B.ORCID, Berger R., Vergote I., D’Incalci M.ORCID, Churruca Galaz C., Chekerov R., Nyvang G. B., Riniker S., Herbertson R., Fossati R., Barretina-Ginesta M. P., Deryal M., Mirza M. R., Biagioli E.ORCID, Iglesias M., Funari G., Romeo M., Tasca G., Pardo B., Tognon G., Rubio-Pérez M. J., DeCensi A., De Giorgi U.ORCID, Zola P., Benedetti Panici P., Aglietta M., Arcangeli V., Zamagni C., Bologna A., Westermann A., Heinzelmann-Schwarz V., Tsibulak I., Wimberger P., Poveda A., Colombo Nicoletta, Gadducci Angiolo, Rulli Eliana, Biagioli Elena, Fossati Roldano, Funari Giuseppe, Carlucci Luciano, Poli Davide, Caudana Maria Clara, Tasca Giulia, Nicoletto Maria Ornella, Tognon Germana, DeCensi Andrea, De Giorgi Ugo, Zola Paolo, Katsaros Dionyssios, Benedetti Panici Pierluigi, Palaia Innocenza, Aglietta Massimo, Arcangeli Valentina, Zamagni Claudio, Bologna Alessandra, Bertolini Alessandro, Caroti Cinzia, Bruzzone Milena, Donadello Nicoletta, Di Costanzo Gianna, Zaniboni Alberto, Surico Daniela, Buosi Roberta, Cortesi Enrico, Zafarana Elena, Fusco Vittorio, Zavallone Laura, Gamucci Teresa, Narducci Filomena, Musacchi Valentina, Babilonti Luciana, Ferrero Annamaria, Cavanna Luigi, Sabbatini Roberto, Tamberi Stefano, Gentili Maria Rosa, Artioli Grazia, Ardizzoia Antonio, Caldara Alessia, Sirotovà Zuzana, Casartelli Clelia, Aieta Michele, Cinieri Saverio, De Marino Elvira, Gori Stefania, Ferraù Francesco, Blasi Livio, Alù Massimiliano, De Placido Sabino, Milandri Carlo, Churruca Galaz Cristina, Barretina-Ginesta Maria Pilar, Bover Isabel, Romeo Margarita, Pardo Beatriz, Rubio-Pèrez Maria Jesus, Poveda Andrés, Santaballa Ana, Márquez Raúl, Alarcon Jesus, Caballero-Diaz Cristina, Ruiz Miravet Nuria, Ortega Eugenia, Arcusa Lanza Maria Angels, Catot Tort Silvia, Garcia Martinez Elena, Girones Regina, Garcia Yolanda, Mendiola Cesar, Sanchez Ana Beatriz, Garcia Martinez Elena, Sehouli Jalid, Deryal Mustafa, Wimberger Pauline, Heinrich Georg, Runnebaum Ingo, Trillsch Fabian, Oskay-Özcelik Gülten, de Wit Maike, Grischke Eva-Maria, Bauerschlag Dirk, Heitz Florian, Mustea Alexander, Fehm Tanja, Heider Andrea, Dieterich Max, Groop-Meier Martina, Battista Marco, Woeckel Achim, Meinhold-Heerlein Ivo, Montes Ana, Herbertson Rebecca, Hudson Emma, Bowen Rebecca, Vergote Ignace, D’Hondt Lionel, Vuylsteke Peter, Vulsteke Christof, Ottevanger Petronella-Beatrix, Westermann Anneke M., Sessa Cristiana, Riniker Salome, Heinzelmann-Schwarz Viola, Von Moos Roger, Kralidis Elena, Mueller Michael, Aebi Stefan, Uhlmann Nussbaum Catrina, Fehr Mathias, Müller Andreas, Taverna Christian, Mäenpää Johanna, Nyvang Gitte-Bettina, Mirza Mansoor Raza, Kristensen Gunnar B., Bentzen Anne Gry, Fiane Bent, Puistola Ulla, Anttila Maarit, Marth Christian, Berger Regina, Petru Edgar, Schauer Christian, Reinthaller Alexander, , , , , , , , , ,
Abstract
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.
Funder
PharmaMar supported the study with an unrestricted grant and provided trabectedin in countries where this drug was not yet reimbursed by the national health system.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology
Reference25 articles.
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