1. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial
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Jacobus Pfisterer, Catherine M Shannon, Klaus Baumann, Joern Rau, Philipp Harter, Florence Joly, Jalid Sehouli, Ulrich Canzler, Barbara Schmalfeldt, Andrew P Dean, Alexander Hein, Alain G Zeimet, Lars C Hanker, Thierry Petit, Frederik Marmé, Ahmed El-Balat, Rosalind Glasspool, Nikolaus de Gregorio, Sven Mahner, Tarek M Meniawy, Tjoung-Won Park-Simon, Marie-Ange Mouret-Reynier, Cristina Costan, Werner Meier, Alexander Reinthaller, Jeffrey C Goh, Tifenn L'Haridon, Sally Baron Hay, Stefan Kommoss, Andreas du Bois, Jean-Emmanuel Kurtz, Sven Ackermann, Christoph Anthuber, Mustafa Aydogdu, Angelika Baldauf, Wolfgang Bauer, Dirk Behringer, Antje Belau, Alexandra Bender, Cosima Brucker, Alexander Burges, Trygve Daabach, Dominik Denschlag, Mustafa Deryal, Steffen Dörfel, Juliane Ebert, Tanja Fehm, Susanne Maria Feidicker, Gabriele Feisel-Schwickardi, Ricardo Felberbaum, Matthias Frank, Gerhard Gebauer, Bernd Gerber, Axel Gerhardt, Andrea Grafe, Martin Griesshammer, Eva-Maria Grischke, Isolde Gröll, Martina Gropp-Meier, Dietrich Hager, Volker Hanf, Carla Verena Hannig, Peer Hantschmann, Tanja Hauzenberger, Uwe Herwig, Martin Heubner, Carsten Hielscher, Felix Hilpert, Thomas Hitschold, Manfred Hofmann, Christian Jackisch, Wolfgang Janni, Ludwig Kiesel, Yon-Dschun Ko, Hans-Joachim Koch, Petra Krabisch, Peter Krieger, Thomas Kubin, Thorsten Kühn, Björn Lampe, Peter Ledwon, Sabine Lemster, Benno Lex, Clemens Liebrich, Ralf Lorenz, Hans-Joachim Lück, Peter Mallmann, Wolfgang Meinerz, Götz Menke, Volker Möbus, Thomas Müller, Volker Müller, Tanja Neunhöffer, Angelika Ober, Gülten Oskay-Özcelik, Horst Ostertag, Martin Pölcher, Beate Rautenberg, Daniel Rein, Wilhelm Reiter, Andreas Rempen, Ingo Runnebaum, Marcus Schmidt, Sabine Schnohr, Heinz Scholz, Willibald Schröder, Eike Simon, Antje Sperfeld, Annette Steckkönig, Hans-Georg Strauß, Ronaldo Stuth, Jürgen Terhaag, Falk Thiel, Marc Thill, Oliver Tomé, Christoph Uleer, Susanne Vogel, Hermann Voß, Michael Weigel, Ulrich Winkler, Arthur Wischnik, Tobias Zeiser, Andreas Zorr, Ros Glasspool, Emma Hudson, Rachel Jones, Judith Lafleur, Christian Marth, Edgar Petru, Yoland Antill, Mary Azer, Sally Baron-Hay, Philip Beale, Stephen Begbie, Allison Black, Karen Briscoe, Andrew Dean, Jeffrey Goh, Sandra Harvey, Chee Lee, Marco Matos, Tarek Meniawy, Inger Olesen, Catherine Shannon, Paul Vasey, Sophie Abadie-Lacourtoisie, Olivier Arsene, Sophie Barthier, Célia Becuwe-Roemer, Dominique Berton-Rigaud, Maria Cappiello-Bataller, Stéphanie Catala, Francesco Del Piano, Gaël Deplanque, Raymond Despax, Nadine Dohollou, Claire Garnier-Tixidré, Julien Grenier, Emmanuel Guardiola, Anne-Claire Hardy-Bessard, Claudia Lefeuvre-Plesse, Marianne Leheurteur, Anne Lesoin, Charles-Briac Levache, Raffaele Longo, Alain Lortholary, Jérôme Meunier, Nadia Raban, Olivier Romano, Jean-Michel Vannetzel, Alain Zannetti, Cancers et préventions, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Obstetrics and Gynecology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of OB/Gyn, University Breast Center Franconia, Univeristy Hospital Erlangen, Goethe-Universität Frankfurt am Main, Mines Nantes (Mines Nantes), Division Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, Universität Heidelberg [Heidelberg] = Heidelberg University, Department of Gynecology, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hannover Medical School [Hannover] (MHH), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Medizinische Universität Wien = Medical University of Vienna, Les Hôpitaux Universitaires de Strasbourg (HUS), Department of Gynaecology, Universität Greifswald - University of Greifswald, University Hospital Düsseldorf, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, University of Rostock, Städtische Kliniken, Department of Gynecology and Obstetrics, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Hämatologie/Onkologie, Klinikum Traunstein, Department of OB/Gyn, Hospital Bayreuth, École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Department of Gynecology and Obstetrics, Center for Integrated Oncology, Bonn University Medical Center, University Hospital Bonn, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Chemical Metals Science Department, Max Planck Institute for Chemical Physics of Solids (CPfS), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Leopold Franzens Universität Innsbruck - University of Innsbruck, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre Hospitalier de Blois (CHB), CRLCC René Gauducheau, Hôpital Saint-Joseph [Marseille], Polyclinique Bordeaux Nord Aquitaine (PBNA), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Armoricain de Radiothérapie, d'Imagerie médicale et d'Oncologie [Plérin, Saint-Brieuc] (CARIO), Department of Medical Oncology, CRLCC Eugène Marquis (CRLCC), Service d'Oncologie Médicale, CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Polyclinique Francheville, Centre Catherine-de-Sienne [Nantes] (CCS), Centre Hospitalier Régional d'Orléans (CHRO), Hématologie clinique [CH Cholet], CH Cholet, Universität Heidelberg [Heidelberg], Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Tübingen [Germany], HESAM Université (HESAM)-HESAM Université (HESAM), University Hospital of Bonn, University of Innsbruck, Centre Hospitalier de Blois (CH Blois), Polyclinique Bordeaux Nord Aquitaine, Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Lille Nord de France (COMUE)-UNICANCER
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0301 basic medicine ,genetic structures ,endocrine system diseases ,[SDV]Life Sciences [q-bio] ,Gastroenterology ,law.invention ,Carboplatin ,Polyethylene Glycols ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Antineoplastic Combined Chemotherapy Protocols ,Clinical endpoint ,Ovarian Neoplasms ,education.field_of_study ,Standard treatment ,Middle Aged ,female genital diseases and pregnancy complications ,3. Good health ,Bevacizumab ,Oncology ,Response Evaluation Criteria in Solid Tumors ,030220 oncology & carcinogenesis ,Austria ,Female ,France ,medicine.drug ,Adult ,medicine.medical_specialty ,Paclitaxel ,Population ,03 medical and health sciences ,Internal medicine ,medicine ,Fallopian Tube Neoplasms ,Humans ,education ,Aged ,Platinum ,business.industry ,Australia ,eye diseases ,Regimen ,030104 developmental biology ,chemistry ,Doxorubicin ,sense organs ,Neoplasm Recurrence, Local ,business - Abstract
Background:\ud State-of-the art therapy for recurrent ovarian cancer suitable for platinum-based re-treatment includes bevacizumab-containing combinations (eg, bevacizumab combined with carboplatin–paclitaxel or carboplatin–gemcitabine) or the most active non-bevacizumab regimen: carboplatin–pegylated liposomal doxorubicin. The aim of this head-to-head trial was to compare a standard bevacizumab-containing regimen versus carboplatin–pegylated liposomal doxorubicin combined with bevacizumab.\ud Methods:\ud This multicentre, open-label, randomised, phase 3 trial, was done in 159 academic centres in Germany, France, Australia, Austria, and the UK. Eligible patients (aged ≥18 years) had histologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube carcinoma with first disease recurrence more than 6 months after first-line platinum-based chemotherapy, and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were stratified by platinum-free interval, residual tumour, previous antiangiogenic therapy, and study group language, and were centrally randomly assigned 1:1 using randomly permuted blocks of size two, four, or six to receive six intravenous cycles of bevacizumab (15 mg/kg, day 1) plus carboplatin (area under the concentration curve [AUC] 4, day 1) plus gemcitabine (1000 mg/m 2, days 1 and 8) every 3 weeks or six cycles of bevacizumab (10 mg/kg, days 1 and 15) plus carboplatin (AUC 5, day 1) plus pegylated liposomal doxorubicin (30 mg/m 2, day 1) every 4 weeks, both followed by maintenance bevacizumab (15 mg/kg every 3 weeks in both groups) until disease progression or unacceptable toxicity. There was no masking in this open-label trial. The primary endpoint was investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy data were analysed in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug. This completed study is registered with ClinicalTrials.gov, NCT01837251.\ud Findings:\ud Between Aug 1, 2013, and July 31, 2015, 682 eligible patients were enrolled, of whom 345 were randomly assigned to receive carboplatin–pegylated liposomal doxorubicin–bevacizumab (experimental group) and 337 were randomly assigned to receive carboplatin–gemcitabine–bevacizumab (standard group). Median follow-up for progression-free survival at data cutoff (July 10, 2018) was 12·4 months (IQR 8·3–21·7) in the experimental group and 11·3 months (8·0–18·4) in the standard group. Median progression-free survival was 13·3 months (95% CI 11·7–14·2) in the experimental group versus 11·6 months (11·0–12·7) in the standard group (hazard ratio 0·81, 95% CI 0·68–0·96; p=0·012). The most common grade 3 or 4 adverse events were hypertension (88 [27%] of 332 patients in the experimental group vs 67 [20%] of 329 patients in the standard group) and neutropenia (40 [12%] vs 73 [22%]). Serious adverse events occurred in 33 (10%) of 332 patients in the experimental group and 28 (9%) of 329 in the standard group. Treatment-related deaths occurred in one patient in the experimental group (
- Published
- 2020
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