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
Authors: Colombo N. , Gadducci A. , Sehouli J. , Rulli E. , Mäenpää J. , Sessa C. , Montes A. , Ottevanger N. B. , Berger R. , Vergote I. , D’Incalci M. , 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. , Iglesias M. , Funari G. , Romeo M. , Tasca G. , Pardo B. , Tognon G. , Rubio-Pérez M. J. , DeCensi A. , De Giorgi U. , Zola P. , Benedetti Panici P. , Aglietta M. , Arcangeli V. , Zamagni C. , Bologna A. , Westermann A. , Heinzelmann-Schwarz V. , Tsibulak I. , Wimberger P. , Poveda A. ,   INOVATYON study group,   Mario Negri Gynecologic Oncology group-MaNGO (MaNGO), 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 ,   Grupo Español de Investigación en Cáncer de Ovario (GEICO), 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 ,   North-Eastern-German Society of Gynaecological Oncology (NOGGO), 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 ,   NHS National Services Scotland, Montes Ana , Herbertson Rebecca , Hudson Emma , Bowen Rebecca ,   Belgian Gynaecological Oncology Group (BGOG), Vergote Ignace , D’Hondt Lionel , Vuylsteke Peter , Vulsteke Christof ,   Dutch Gynaecological Oncology Group (DGOG), Ottevanger Petronella-Beatrix , Westermann Anneke M. ,   Swiss Group for Clinical Cancer Research (SAKK), 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 ,   Nordic Society of Gynaecological Oncology (NSGO), Mäenpää Johanna , Nyvang Gitte-Bettina , Mirza Mansoor Raza , Kristensen Gunnar B. , Bentzen Anne Gry , Fiane Bent , Puistola Ulla , Anttila Maarit ,   AGO Studienzentrale (AGO-Austria), Marth Christian , Berger Regina , Petru Edgar , Schauer Christian , Reinthaller Alexander 
Published: February 2023

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.