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

Research output: Contribution to journalArticle

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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Ovarian Neoplasms
Placebos
Drug Therapy
Carboplatin
Paclitaxel
Gynecology
Obstetrics
Disease-Free Survival
Research Personnel
Platelet-Derived Growth Factor Receptors
Fibroblast Growth Factor Receptors
Vascular Endothelial Growth Factor Receptor
nintedanib
Double-Blind Method
Area Under Curve
Disease Progression
Diarrhea
Therapeutics
Population

ASJC Scopus subject areas

  • Oncology

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Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12) : A randomised, double-blind, placebo-controlled phase 3 trial. / Bois, Andreas du; Kristensen, Gunnar; Ray-Coquard, Isabelle; Reuss, Alexander; Pignata, Sandro; Colombo, Nicoletta; Denison, Ursula; Vergote, Ignace; Del Campo, Jose; Ottevanger, P. B.; Heubner, Martin; Minarik, Thomas; Sevin, Emmanuel; De Gregorio, Nikolaus; Bidzinski, Mariusz; Pfisterer, J.; Malander, Susanne; Hilpert, Felix; Mirza, Mansoor Raza; Scambia, Giovanni; Meier, Werner; Nicoletto, Maria Ornella; Bjorge, Line; Lortholary, Alain; Sailer, Martin Oliver; Merger, Michael; Harter, Philipp.

In: The Lancet Oncology, Vol. 17, No. 1, 01.01.2016, p. 78-89.

Research output: Contribution to journalArticle

Bois, AD, Kristensen, G, Ray-Coquard, I, Reuss, A, Pignata, S, Colombo, N, Denison, U, Vergote, I, Del Campo, J, Ottevanger, PB, Heubner, M, Minarik, T, Sevin, E, De Gregorio, N, Bidzinski, M, Pfisterer, J, Malander, S, Hilpert, F, Mirza, MR, Scambia, G, Meier, W, Nicoletto, MO, Bjorge, L, Lortholary, A, Sailer, MO, Merger, M & 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, vol. 17, no. 1, pp. 78-89. https://doi.org/10.1016/S1470-2045(15)00366-6
Bois, Andreas du ; Kristensen, Gunnar ; Ray-Coquard, Isabelle ; Reuss, Alexander ; Pignata, Sandro ; Colombo, Nicoletta ; Denison, Ursula ; Vergote, Ignace ; Del Campo, Jose ; Ottevanger, P. B. ; Heubner, Martin ; Minarik, Thomas ; Sevin, Emmanuel ; De Gregorio, Nikolaus ; Bidzinski, Mariusz ; Pfisterer, J. ; Malander, Susanne ; Hilpert, Felix ; Mirza, Mansoor Raza ; Scambia, Giovanni ; Meier, Werner ; Nicoletto, Maria Ornella ; Bjorge, Line ; Lortholary, Alain ; Sailer, Martin Oliver ; Merger, Michael ; Harter, Philipp. / Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12) : A randomised, double-blind, placebo-controlled phase 3 trial. In: The Lancet Oncology. 2016 ; Vol. 17, No. 1. pp. 78-89.
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T1 - Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12)

T2 - A randomised, double-blind, placebo-controlled phase 3 trial

AU - Bois, Andreas du

AU - Kristensen, Gunnar

AU - Ray-Coquard, Isabelle

AU - Reuss, Alexander

AU - Pignata, Sandro

AU - Colombo, Nicoletta

AU - Denison, Ursula

AU - Vergote, Ignace

AU - Del Campo, Jose

AU - Ottevanger, P. B.

AU - Heubner, Martin

AU - Minarik, Thomas

AU - Sevin, Emmanuel

AU - De Gregorio, Nikolaus

AU - Bidzinski, Mariusz

AU - Pfisterer, J.

AU - Malander, Susanne

AU - Hilpert, Felix

AU - Mirza, Mansoor Raza

AU - Scambia, Giovanni

AU - Meier, Werner

AU - Nicoletto, Maria Ornella

AU - Bjorge, Line

AU - Lortholary, Alain

AU - Sailer, Martin Oliver

AU - Merger, Michael

AU - Harter, Philipp

N1 - già in RC 2015, inserito anche in SIPS

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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 [

AB - 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 [

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