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 M del Campo, Petronella Ottevanger, Martin Heubner, Thomas Minarik, Emmanuel Sevin, Nikolaus de Gregorio, Mariusz Bidziński, Jacobus Pfisterer, Susanne Malander, Felix Hilpert, Mansoor R Mirza, Giovanni ScambiaWerner Meier, Maria O Nicoletto, Line Bjørge, Alain Lortholary, Martin Oliver Sailer, Michael Merger, Philipp Harter, Massimo Candiani, Giorgia Mangili

Research output: Contribution to journalArticlepeer-review

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

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology

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