Scientific publications

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

Aug 5, 2019 | Magazine: International Journal of Cancer

Ray-Coquard I (1), Cibula D (2), Mirza MR (3), Reuss A (4), Ricci C (5), Colombo N (6), Koch H (7), Goffin F (8), González-Martin A (9), Ottevanger PB 10, Baumann K (11), Bjørge L (12), Lesoin A (13), Burges A (14), Rosenberg P (15), Gropp-Meier M (16), Harrela M (17), Harter P (18), Frenel JS (19), Minarik T (20), Pisano C (21), Hasenburg A (22), Merger M (23), du Bois A (18); AGO Study Group-led GCIG/ENGOT Intergroup Consortium.

(1) GINECO and Medical Oncology Department, Centre Léon Bérard, University Claude Bernard Lyon, Lyon, France.
(2) AGO and Oncogynecologic Center, Department of Obstetrics and Gynecology, General Faculty Hospital, Charles University of Prague, Prague, Czech Republic.
(3) NSGO and Department of Oncology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark.
(4) AGO and Coordinating Center for Clinical Trials, Philipps-University of Marburg, Marburg, Germany.
(5) MITO and Division of Gynecologic Oncology, Department of Women and Children's Health and Public Health, Fondazione Policlinico Gemelli IRCCS, Rome, Italy.
(6) MaNGO and European Institute of Oncology and University of Milan Bicocca, Milan, Italy.
(7) AGO Austria and Department of Obstetrics and Gynecology, Paracelsus Medical University, Salzburg, Austria.
(8) BGOG and CHU de Liège, University of Liège, Liège, Belgium.
(9) GEICO and Medical Oncology Department, Clínica Universidad de Navarra, Madrid, Spain.
(10) DGOG and Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands.
(11) AGO and Department of Gynecology, Klinikum der Stadt Ludwigshafen GmbH, Ludwigshafen, Germany.
(12) NSGO and Department of Gynecology, Haukeland Universitetssykehus, Bergen, and Center for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.
(13) GINECO and Department of Gynecologic Cancer and Medical Oncology, Centre Oscar Lambret, Lille, France.
(14) AGO and Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Germany.
(15) NSGO and Department of Oncology, University Hospital Linköping, Linköping, Sweden.
(16) AGO and Department of Gynecology and Obstetrics, Oberschwabenklinik, Krankenhaus St. Elisabeth, Ravensburg, Germany.
(17) NSGO and Department of Gynoncology and Gynecology and Obstetrics, Kymenlaakso Central Hospital, Kotka, Finland.
(18) AGO and Department of Gynecology and Gynecologic Oncology, Kliniken Essen Mitte, Essen, Germany.
(19)GINECO and Centre René Gauducheau, Institut de Cancerologie de l'Ouest, Saint Herblain, France.
(20) NSGO and National Institute of Oncology, Bratislava, Slovakia.
(21) MITO and Department of Uro-Gynecologic Oncology, Istituto Nazionale per Io Studio e la Cura dei Tumori 'Fondazione G. Pascale' IRCCS, Napoli, Italy.
(22) AGO and Department of Obstetrics and Gynecology, University Medical Center, Mainz, Germany.
(23) Oncology Medicine, Boehringer Ingelheim International GmbH, Biberach, Germany.


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 end point) compared with placebo. We report final results, including overall survival (OS). Patients with primary debulked International Federation of Gynecology 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, 1366 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 versus 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 non-high-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.

CITATION  Int J Cancer. 2019 Aug 5. doi: 10.1002/ijc.32606