Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): A randomised, double-blind, placebo-controlled phase 3 trial

Andreas du Bois, Gunnar Kristensen, Isabelle Ray-Coquard, Alexander Reuss, Sandro Pignata, Nicoletta Colombo, Ursula Denison, Ignace Vergote, Jose Del Campo, P. B. Ottevanger, Martin Heubner, Thomas Minarik, Emmanuel Sevin, Nikolaus De Gregorio, Mariusz Bidzinski, J. Pfisterer, Susanne Malander, Felix Hilpert, Mansoor Raza Mirza, Giovanni ScambiaWerner Meier, Maria Ornella Nicoletto, Line Bjorge, Alain Lortholary, Martin Oliver Sailer, Michael Merger, Philipp Harter

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Abstract

Background: Angiogenesis is a target in the treatment of ovarian cancer. Nintedanib, an oral triple angiokinase inhibitor of VEGF receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, has shown activity in phase 2 trials in this setting. We investigated the combination of nintedanib with standard carboplatin and paclitaxel chemotherapy in patients with newly diagnosed advanced ovarian cancer. Methods: In this double-blind phase 3 trial, chemotherapy-naive patients (aged 18 years or older) with International Federation of Gynecology and Obstetrics (FIGO) IIB-IV ovarian cancer and upfront debulking surgery were stratified by postoperative resection status, FIGO stage, and planned carboplatin dose. Patients were randomly assigned (2:1) via an interactive voice or web-based response system to receive six cycles of carboplatin (AUC 5 mg/mL per min or 6 mg/mL per min) and paclitaxel (175 mg/m2) in addition to either 200 mg of nintedanib (nintedanib group) or placebo (placebo group) twice daily on days 2-21 of every 3-week cycle for up to 120 weeks. Patients, investigators, and independent radiological reviewers were masked to treatment allocation. The primary endpoint was investigator-assessed progression-free survival analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01015118. Findings: Between Dec 9, 2009, and July 27, 2011, 1503 patients were screened and 1366 randomly assigned by nine study groups in 22 countries: 911 to the nintedanib group and 455 to the placebo group. 486 (53%) of 911 patients in the nintedanib group experienced disease progression or death compared with 266 (58%) of 455 in the placebo group. Median progression-free survival was significantly longer in the nintedanib group than in the placebo group (17·2 months [95% CI 16·6-19·9] vs 16·6 months [13·9-19·1]; hazard ratio 0·84 [95% CI 0·72-0·98]; p=0·024). The most common adverse events were gastrointestinal (diarrhoea: nintedanib group 191 [21%] of 902 grade 3 and three [

Original languageEnglish
Pages (from-to)78-89
Number of pages12
JournalThe Lancet Oncology
Volume17
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

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ASJC Scopus subject areas

  • Oncology

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Bois, A. D., Kristensen, G., Ray-Coquard, I., Reuss, A., Pignata, S., Colombo, N., Denison, U., Vergote, I., Del Campo, J., Ottevanger, P. B., Heubner, M., Minarik, T., Sevin, E., De Gregorio, N., Bidzinski, M., Pfisterer, J., Malander, S., Hilpert, F., Mirza, M. R., ... Harter, P. (2016). Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): A randomised, double-blind, placebo-controlled phase 3 trial. The Lancet Oncology, 17(1), 78-89. https://doi.org/10.1016/S1470-2045(15)00366-6