Final results from GCIG/ENGOT/AGO-OVAR 12, a randomised placebo-controlled phase III trial of nintedanib combined with chemotherapy for newly diagnosed advanced ovarian cancer.
Ray-Coquard, Isabelle; Cibula, David; Mirza, Mansoor Ret al.
2020 • In International Journal of Cancer, 146 (2), p. 439 - 448
[en] AGO-OVAR 12 investigated the effect of adding the oral triple angiokinase inhibitor nintedanib to standard front-line chemotherapy for advanced ovarian cancer. At the primary analysis, nintedanib demonstrated significantly improved progression-free survival (PFS; primary endpoint) compared with placebo. We report final results, including overall survival (OS). Patients with primary debulked International Federation of Gynaecology and Obstetrics (FIGO) stage IIB-IV newly diagnosed ovarian cancer were randomised 2:1 to receive carboplatin (area under the curve 5 or 6) plus paclitaxel (175 mg/m2 ) on day 1 every 3 weeks for six cycles combined with either nintedanib 200 mg or placebo twice daily on days 2-21 every 3 weeks for up to 120 weeks. Between December 2009 and July 2011, 1,366 patients were randomised (911 to nintedanib, 455 to placebo). Disease was considered as high risk (FIGO stage III with >1 cm residuum, or any stage IV) in 39%. At the final analysis, 605 patients (44%) had died. There was no difference in OS (hazard ratio 0.99, 95% confidence interval [CI] 0.83-1.17, p = 0.86; median 62.0 months with nintedanib vs. 62.8 months with placebo). Subgroup analyses according to stratification factors, clinical characteristics and risk status showed no OS difference between treatments. The previously reported PFS improvement seen with nintedanib did not translate into an OS benefit in the nonhigh-risk subgroup. Updated PFS results were consistent with the primary analysis (hazard ratio 0.86, 95% CI 0.75-0.98; p = 0.029) favouring nintedanib. The safety profile was consistent with previous reports.
Disciplines :
Oncology
Author, co-author :
Ray-Coquard, Isabelle ; GINECO and Medical Oncology Department, Centre Léon Bérard, University Claude Bernard Lyon, Lyon, France
Cibula, David; AGO and Oncogynecologic Center, Department of Obstetrics and Gynecology, General Faculty Hospital, Charles University of Prague, Prague, Czech Republic
Mirza, Mansoor R; NSGO and Department of Oncology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark
Reuss, Alexander; AGO and Coordinating Center for Clinical Trials, Philipps-University of Marburg, Marburg, Germany
Ricci, Caterina; MITO and Division of Gynecologic Oncology, Department of Women and Children's Health and Public Health, Fondazione Policlinico Gemelli IRCCS, Rome, Italy
Colombo, Nicoletta; MaNGO and European Institute of Oncology and University of Milan Bicocca, Milan, Italy
Koch, Horst; AGO Austria and Department of Obstetrics and Gynecology, Paracelsus Medical University, Salzburg, Austria
Goffin, Frédéric ; Centre Hospitalier Universitaire de Liège - CHU > > Service de gynécologie-obstétrique (CHR)
González-Martin, Antonio; GEICO and Medical Oncology Department, Clínica Universidad de Navarra, Madrid, Spain
Ottevanger, Petronella B; DGOG and Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands
Baumann, Klaus; AGO and Department of Gynecology, Klinikum der Stadt Ludwigshafen GmbH, Ludwigshafen, Germany
Bjørge, Line; NSGO and Department of Gynecology, Haukeland Universitetssykehus, Bergen, Norway ; Center for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway
Lesoin, Anne; GINECO and Department of Gynecologic Cancer and Medical Oncology, Centre Oscar Lambret, Lille, France
Burges, Alexander; AGO and Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Germany
Rosenberg, Per; NSGO and Department of Oncology, University Hospital Linköping, Linköping, Sweden
Gropp-Meier, Martina; AGO and Department of Gynecology and Obstetrics, Oberschwabenklinik, Krankenhaus St. Elisabeth, Ravensburg, Germany
Harrela, Maija; NSGO and Department of Gynoncology and Gynecology and Obstetrics, Kymenlaakso Central Hospital, Kotka, Finland
Harter, Philipp; AGO and Department of Gynecology and Gynecologic Oncology, Kliniken Essen Mitte, Essen, Germany
Frenel, Jean-Sébastien; GINECO and Centre René Gauducheau, Institut de Cancerologie de l'Ouest, Saint Herblain, France
Minarik, Tomas; NSGO and National Institute of Oncology, Bratislava, Slovakia
Pisano, Carmela; MITO and Department of Uro-Gynecologic Oncology, Istituto Nazionale per Io Studio e la Cura dei Tumori 'Fondazione G. Pascale' IRCCS, Naples, Italy
Hasenburg, Annette; AGO and Department of Obstetrics and Gynecology, University Medical Center, Mainz, Germany
Merger, Michael; Oncology Medicine, Boehringer Ingelheim International GmbH, Biberach, Germany
du Bois, Andreas; AGO and Department of Gynecology and Gynecologic Oncology, Kliniken Essen Mitte, Essen, Germany
AGO Study Group-led GCIG/ENGOT Intergroup Consortium
Final results from GCIG/ENGOT/AGO-OVAR 12, a randomised placebo-controlled phase III trial of nintedanib combined with chemotherapy for newly diagnosed advanced ovarian cancer.
The authors thank all the patients and their families who participated in this trial; all investigators and supporters at the study sites; the central study offices of the study groups; Behnaz Aminossadati, the data manager of the Coordinating Center for Clinical Trials, Philipps-University of Marburg (Marburg, Germany); and all involved staff at Boehringer Ingelheim. Michael Bookman (chair), Martin Gore (†), Michael Friedlander, Gavin Stuart and Emmanuel Lesaffre (biostatistician) were members of the data monitoring committee. The following cooperative academic study groups (in alphabetical order) performed the trial: AGO Study Group (referred to as “AGO”; leading group) and AGO Austria, BGOG Belgium and Luxembourg, DGOG The Netherlands, GEICO Spain, GINECO France, MaNGO Italy, MITO Italy and NSGO Scandinavia. Medical writing support was provided by Jennifer Kelly, MA (Medi-Kelsey Ltd, Ashbourne, UK) funded by AGO. This work was supported by Boehringer Ingelheim, Ingelheim, Germany (no grant number applicable).
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