Medline ® Abstract for Reference 22
of 'Medical treatment for relapsed epithelial ovarian, fallopian tubal, or peritoneal cancer: Platinum-resistant disease'
Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial.
Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I
J Clin Oncol. 2014;32(13):1302. Epub 2014 Mar 17.
PURPOSE: In platinum-resistant ovarian cancer (OC), single-agent chemotherapy is standard. Bevacizumab is active alone and in combination. AURELIA is the first randomized phase III trial to our knowledge combining bevacizumab with chemotherapy in platinum-resistant OC.
PATIENTS AND METHODS: Eligible patients had measurable/assessable OC that had progressed<6 months after completing platinum-based therapy. Patients with refractory disease, history of bowel obstruction, or>two prior anticancer regimens were ineligible. After investigators selected chemotherapy (pegylated liposomal doxorubicin, weekly paclitaxel, or topotecan), patients were randomly assigned to single-agent chemotherapy alone or with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until progression, unacceptable toxicity, or consent withdrawal. Crossover to single-agent bevacizumab was permitted after progression with chemotherapy alone. The primary end point was progression-free survival (PFS) by RECIST. Secondary end points included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes.
RESULTS: The PFS hazard ratio (HR) after PFS events in 301 of 361 patients was 0.48 (95% CI, 0.38 to 0.60; unstratified log-rank P<.001). Median PFS was 3.4 months with chemotherapy alone versus 6.7 months with bevacizumab-containing therapy. RECIST ORR was 11.8% versus 27.3%, respectively (P = .001). The OS HR was 0.85 (95% CI, 0.66 to 1.08; P<.174; median OS, 13.3 v 16.6 months, respectively). Grade≥2 hypertension and proteinuria were more common with bevacizumab. GI perforation occurred in 2.2% of bevacizumab-treated patients.
CONCLUSION: Adding bevacizumab to chemotherapy statistically significantly improved PFS and ORR; the OS trend was not significant. No new safety signals were observed.
Eric Pujade-Lauraine, Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) and UniversitéParis Descartes, Assistance Publique-Hôpitaux de Paris, Paris; Béatrice Weber, GINECO and Centre Alexis Vautrin, Vandoeuvre-les-Nancy; Philippe Follana, GINECO and Centre Antoine-Lacassagne, Nice; Isabelle Ray-Coquard, GINECO and Centre Léon Bérard, Lyon, France; Felix Hilpert, Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) and Klinik für Gynäkologie und Geburtshilfe, Kiel; Alexander Reuss, AGO and Coordinating Center for Clinical Trials, Marburg; Pauline Wimberger, AGO and University of Duisburg-Essen, Essen, Germany; Andres Poveda, Grupo Español de Investigación en Cáncer de Ovario (GEICO) and Instituto Valenciano de Oncologia, Valencia; Ana Oaknin, GEICO and Vall d'Hebron University Hospital, Barcelona, Spain; Gunnar Kristensen, Nordic Society of Gynaecological Oncology (NSGO) and Norwegian Radium Hospital, Oslo, Norway; Roberto Sorio, Multicenter Italian Trials in Ov