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
Nicoletta Colombo, Angiolo Gadducci, Jalid Sehouli, Eliana Rulli, Johanna Mäenpää, Cristiana Sessa, Ana Fernández Montés, Nelleke Ottevanger, Regina Berger, Ignace Vergote, Maurizio D’Incalci, Cristina Churruca Galaz, Radoslav Chekerov, Gitte-Bettina Nyvang, Salome Riniker, Rebecca Herbertson, Roldano Fossati, Maria Pilar Barretina-Ginesta, Mustafa Deryal, Mansoor Raza Mirza, Elena Biagioli, M. Iglesias, Giuseppe Funari, Margarita Romeo, Giulia Tasca, Beatriz Pardo, Germana Tognon, María Jesús Rubio-Pérez, Andrea DeCensi, Ugo De Giorgi, Paolo Zola, P. Benedetti Panici, Massimo Aglietta, Valentina Arcangeli, Claudio Zamagni, Alessandra Bologna, Anneke M. Westermann, Viola Heinzelmann‐Schwarz, I. Tsibulak, Pauline Wimberger, Andrés Poveda, A. Poveda, INOVATYON study group, Nicoletta Colombo, Angiolo Gadducci, Eliana Rulli, Elena Biagioli, Roldano Fossati, Giuseppe Funari, Luciano Carlucci, Davide Poli, Maria Clara Caudana, Giulia Tasca, Maria Ornella Nicoletto, Germana Tognon, Andrea DeCensi, Ugo De Giorgi, Paolo Zola, Dionyssios Katsaros, Pierluigi Benedetti Panici, Innocenza Palaia, Massimo Aglietta, Valentina Arcangeli, Claudio Zamagni, Alessandra Bologna, Alessandro Bertolini, C. Caroti, Milena Bruzzone, Nicoletta Donadello, Gianna Di Costanzo, Alberto Zaniboni, Daniela Surico, R. Buosi, Enrico Cortesi, Elena Zafarana, Vittorio Fusco, Laura Zavallone, Teresa Gamucci, Filomena Narducci, Valentina Musacchi, L Babilonti, Annamaria Ferrero, Luigi Cavanna, Roberto Sabbatini, Stefano Tamberi, Maria Rosa Gentili, Grazia Artioli, Antonio Ardizzoia, A. Caldara, Zuzana Sirotovà, Clelia Casartelli, Michele Aieta, Saverio Cinieri, Elvira De Marino, Stefania Gori, Francesco Ferraù, Livio Blasi, Massimiliano Alù, Sabino De Placido, Carlo Milandri
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.