title: Efficacy and Safety of Bevacizumab-Containing Therapy in Newly Diagnosed Ovarian Cancer: ROSiA Single-Arm Phase 3B Study.
abstract: The aim of this study was to assess the safety and efficacy of extending bevacizumab therapy beyond 15 months in nonprogressive ovarian cancer.
  
  
  
  In this multinational prospective single-arm study (ClinicalTrials.gov NCT01239732), eligible patients had International Federation of Gynecology and Obstetrics stage IIB to IV or grade 3 stage I to IIA ovarian cancer without clinical signs or symptoms of gastrointestinal obstruction or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the preceding 6 months. Prior neoadjuvant chemotherapy was permitted. After debulking surgery, patients received bevacizumab 15 (or 7.5) mg/kg every 3 weeks (q3w) with 4 to 8 cycles of paclitaxel (investigator's choice of 175 mg/m q3w or 80 mg/m weekly) plus carboplatin AUC 5 to 6 q3w. Single-agent bevacizumab was continued until progression or for up to 24 months. The primary end point was safety.
  
  
  
  Between December 2010 and May 2012, 1021 patients from 35 countries began study treatment. Bevacizumab was administered at 15 mg/kg in 89% of patients and for more than 15 months in 53%. Median follow-up duration was 32 months (range, 1-50 months). The most common all-grade adverse events were hypertension (55% of patients), neutropenia (49%), and alopecia (43%). The most common grade 3 or higher-grade adverse events were neutropenia (27%) and hypertension (25%). Bevacizumab was discontinued because of proteinuria in 5% of patients and hypertension in 3%. Median progression-free survival (PFS) was 25.5 months (95% confidence interval, 23.7-27.6 months).
  
  
  
  Extended bevacizumab demonstrated increased incidences of proteinuria and hypertension compared with 12 or 15 months of bevacizumab in previous trials, but these rarely led to bevacizumab discontinuation. Median PFS is the longest reported for frontline bevacizumab-containing therapy. The longer bevacizumab duration beyond 15 months in this study may improve PFS without substantially compromising safety.
authors.affiliation: *Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada; †Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, and Alliance Pour la Recherche en Cancérologie, Paris, France; ‡Chemotherapy Department of State Budgetary Healthcare Institution, Clinical Oncology Dispensary #1, Krasnodar Region Ministry of Healthcare, Krasnodar, Russia; §Gynecologic Oncology Department, Sheba Medical Center, Tel Hashomer, Israel; ∥University Hospital 12 de Octubre, Madrid, Spain; ¶Medical Department, Gustave Roussy, Villejuif, France; #Department of Clinical Oncology, Oncology Center Prof. F. Lukaszczyka, Bydgoszcz, Poland; **Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece; ††Ente Ospedaliero Ospedali Galliera, Genoa, Italy; ‡‡Riga East University Hospital, Latvian Oncology Centre, Riga, Latvia; §§Medical Oncology Department, MD Anderson Cancer Center Madrid, Madrid, Spain; ∥∥Pérola Byington Hospital/Faculty of Medicine University of São Paulo, São Paulo, Brazil; ¶¶Medical Oncology Department, Centre François Baclesse, Caen, France; ##Policlinico Sant'Orsola-Malpighi, Bologna, Italy; ***Division of Gynecology and Obstetrics, Department of Experimental and Clinical Medicine, University of Pisa, Pisa, Italy; †††Global Medical Affairs, F. Hoffmann-La Roche Ltd, Basel, Switzerland; and ‡‡‡Division of Medical Gynecologic Oncology, European Institute of Oncology and University of Milano-Bicocca, Milan, Italy.
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
authors.forename: Frédéric
authors.initials: F
authors.lastname: Selle
authors.forename: Irina
authors.initials: I
authors.lastname: Davidenko
authors.forename: Jacob
authors.initials: J
authors.lastname: Korach
authors.forename: Cesar
authors.initials: C
authors.lastname: Mendiola
authors.forename: Patricia
authors.initials: P
authors.lastname: Pautier
authors.forename: Ewa
authors.initials: E
authors.lastname: Chmielowska
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Bamias
authors.forename: Andrea
authors.initials: A
authors.lastname: DeCensi
authors.forename: Zanete
authors.initials: Z
authors.lastname: Zvirbule
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Martín
authors.forename: Roberto
authors.initials: R
authors.lastname: Hegg
authors.forename: Florence
authors.initials: F
authors.lastname: Joly
authors.forename: Claudio
authors.initials: C
authors.lastname: Zamagni
authors.forename: Angiolo
authors.initials: A
authors.lastname: Gadducci
authors.forename: Nicolas
authors.initials: N
authors.lastname: Martin
authors.forename: Stephen
authors.initials: S
authors.lastname: Robb
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Colombo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D000077216:Carcinoma, Ovarian Epithelial; D004334:Drug Administration Schedule; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010534:Peritoneal Neoplasms / Q000188:drug therapy; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel