JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T Randomized Controlled Trial Testing the Efficacy of Platinum-Free Interval Prolongation in Advanced Ovarian Cancer: The MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG Study Sandro Pignata, Giovanni Scambia, Alessandra Bologna, Simona Signoriello, Ignace B. Vergote, Uwe Wagner, Domenica Lorusso, Viviana Murgia, Roberto Sorio, Gabriella Ferrandina, Cosimo Sacco, Gennaro Cormio, Enrico Breda, Saverio Cinieri, Donato Natale, Giorgia Mangili, Carmela Pisano, Sabrina Chiara Cecere, Marilena Di Napoli, Vanda Salutari, Francesco Raspagliesi, Laura Arenare, Alice Bergamini, Jane Bryce, Gennaro Daniele, Maria Carmela Piccirillo, Ciro Gallo, and Francesco Perrone A B S T R A C T Purpose Platinum-based chemotherapy (PBC) for patients with progressing ovarian cancer (OC) is more effective with a longer time interval from previous platinum treatment (platinum-free interval [PFI]). In 1999, it was hypothesized that prolonging PFI with single-agent non-PBC (NPBC) may offer a strategy to improve overall outcome. MITO-8 aimed to verify this hypothesis commonly used in clinical practice although it has not been prospectively tested. Methods MITO-8 is an open-label, prospective, randomized, superiority trial. Patients with OC who experienced disease progression 6 to 12 months after their last platinum treatment were randomly assigned 1:1 to the experimental sequence of NPBC followed by PBC at subsequent relapse or the standard reverse treatment sequence. Overall survival (OS) was the primary end point. Results Two hundred fifteen patients were enrolled (standard arm [n = 108]; experimental arm [n = 107]). The trial ended before planned because of slow enrollment. PFI was prolonged in the experimental arm (median, 7.8 v 0.01 months). There was no OS benefit in the experimental arm (median, 21.8 v 24.5 months; hazard ratio, 1.38; 95% CI, 0.99 to 1.94; P = .06). Progression-free survival after the sequence was significantly shorter in the experimental arm (median, 12.8 v 16.4 months; hazard ratio, 1.41; 95% CI, 1.04 to 1.92; P = .025). Global quality-of-life change after three cycles was worse in the experimental arm. Slight differences were observed in the incidence of adverse effects. Conclusion MITO-8 supports the recommendation that PBC not be delayed in favor of an NPBC in patients with partially platinum-sensitive OC. PBC should be used as a control arm in future trials of new drugs in this setting. J Clin Oncol 35:3347-3353. © 2017 by American Society of Clinical Oncology INTRODUCTION Most patients with ovarian cancer (OC) experi- ence disease progression after primary surgery and first-line platinum-based chemotherapy (PBC) and require subsequent treatment. Retreat- ment with PBC is possible—the effectiveness of treatment with PBC increases with a longer interval from the initial PBC treatment. 1,2 Therefore, the time from last platinum treatment to recurrence (platinum-free interval [PFI]) drives a treatment strategy that is based on nonplatinum chemother- apy if PFI is , 6 months (platinum resistant), and on platinum-containing doublets if PFI is . 12 months (platinum sensitive). There is un- certainty when the PFI is between 6 and 12 months (partially platinum sensitive) because of un- satisfactory results from treatment with platinum- containing doublets. Author affiliations and support information (if applicable) appear at the end of this article. Published at jco.org on August 21, 2017. Clinical trial information: NCT00657878, EudraCT number 2008-001755-22. Corresponding author: Sandro Pignata, MD, Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Pascale IRCCS, via Mariano Semmola, 80131 Naples, Italy; e-mail: s.pignata@ istitutotumori.na.it. © 2017 by American Society of Clinical Oncology 0732-183X/17/3529w-3347w/$20.00 ASSOCIATED CONTENT Appendix DOI: https://doi.org/10.1200/JCO. 2017.73.4293 Data Supplement DOI: https://doi.org/10.1200/JCO. 2017.73.4293 DOI: https://doi.org/10.1200/JCO.2017. 73.4293 © 2017 by American Society of Clinical Oncology 3347 VOLUME 35 • NUMBER 29 • OCTOBER 10, 2017 Downloaded from ascopubs.org by 52.90.80.35 on June 18, 2022 from 052.090.080.035 Copyright © 2022 American Society of Clinical Oncology. All rights reserved.