title: Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Adding bevacizumab to chemotherapy statistically significantly improved PFS and ORR; the OS trend was not significant. No new safety signals were observed.
authors.affiliation: Eric Pujade-Lauraine, Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) and Université Paris 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 Ovarian Cancer and Istituto di Ricovero e Cura a Carattere Scientifico, Aviano, Italy; Ignace Vergote, Belgian Gynaecological Oncology Group and University Hospital Leuven, Leuven, Belgium; Petronella Witteveen, Dutch Gynecological Oncology Group and University Medical Center Utrecht, Utrecht, the Netherlands; Aristotelis Bamias, Hellenic Cooperative Oncology Group and University of Athens, Athens, Greece; Deolinda Pereira, GINECO and Instituto Português de Oncologia do Porto, Porto, Portugal; Mansoor Raza Mirza, NSGO and Rigshospitalet, Copenhagen, Denmark; and David Bollag, F. Hoffmann-La Roche, Basel, Switzerland.
authors.forename: Eric
authors.initials: E
authors.lastname: Pujade-Lauraine
authors.forename: Felix
authors.initials: F
authors.lastname: Hilpert
authors.forename: Béatrice
authors.initials: B
authors.lastname: Weber
authors.forename: Alexander
authors.initials: A
authors.lastname: Reuss
authors.forename: Andres
authors.initials: A
authors.lastname: Poveda
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kristensen
authors.forename: Roberto
authors.initials: R
authors.lastname: Sorio
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.forename: Petronella
authors.initials: P
authors.lastname: Witteveen
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Bamias
authors.forename: Deolinda
authors.initials: D
authors.lastname: Pereira
authors.forename: Pauline
authors.initials: P
authors.lastname: Wimberger
authors.forename: Ana
authors.initials: A
authors.lastname: Oaknin
authors.forename: Mansoor Raza
authors.initials: MR
authors.lastname: Mirza
authors.forename: Philippe
authors.initials: P
authors.lastname: Follana
authors.forename: David
authors.initials: D
authors.lastname: Bollag
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ray-Coquard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; C506643:liposomal doxorubicin; D000068258:Bevacizumab; D011092:Polyethylene Glycols; D019772:Topotecan; D004317:Doxorubicin; D017239:Paclitaxel