title: Progression-free survival by local investigator versus independent central review: comparative analysis of the AGO-OVAR16 Trial.
abstract: BACKGROUND
  Analysis of progression-free survival (PFS) as the primary endpoint in advanced epithelial ovarian, fallopian tube, and primary peritoneal cancer (AEOC) trials may be confounded by the difficulty of radiologic evaluation of disease progression and the potential for discrepancy between investigator and blinded independent central assessments. PFS as assessed by local investigator (INV) was the primary endpoint of AGO-OVAR16, a randomized, double-blind trial of pazopanib maintenance therapy in AEOC. To confirm the robustness of the primary analysis, PFS was also evaluated by blinded independent central review (BICR).
  
  
  METHODS
  Patients with histologically confirmed AEOC (N = 940) were randomized 1:1 to receive pazopanib 800 mg/day or placebo for up to 24 months. Tumor response in the intent-to-treat population was evaluated by CT/MRI every 6 months and analyzed per RECIST 1.0.
  
  
  RESULTS
  Pazopanib prolonged PFS versus placebo by INV (median 17.9 vs 12.3 months; hazard ratio [HR] = 0.766, 95% confidence interval [CI]: 0.643-0.911; P = 0.0021). Results for PFS by BICR were similar (median 15.4 vs 11.8 months; HR = 0.802, 95% CI: 0.678-0.949; P = 0.0084). Progression events were recorded later by INV in 23% of pazopanib-treated patients and 17% of placebo-treated patients. The overall concordance between INV and BICR assessments was 84% and 86% in the pazopanib and placebo arms, respectively.
  
  
  CONCLUSIONS
  By INV and BICR assessments, maintenance therapy with pazopanib in AEOC provided a significantly longer PFS than placebo. The good overall concordance between INV and BICR assessments, as well as HR and P value consistency, supports the reliability of investigator-assessed PFS as the primary endpoint in AGO-OVAR16.
authors.affiliation: Institut Bergonié, Bordeaux, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Floquet
authors.affiliation: University Hospitals Leuven, Dept. of Gynaecological Oncology, Leuven, Belgium.
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.affiliation: University of Milan Bicocca and European Institute of Oncology, Gynecologic Oncology, Milan, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Colombo
authors.affiliation: Department of Gynecology and Gynecologic Oncology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Bent
authors.initials: B
authors.lastname: Fiane
authors.affiliation: Creighton University School of Medicine at St. Joseph's Hospital and Medical Center, Division of Gynecologic Oncology, Phoenix, AZ, USA.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
authors.affiliation: Allgemeines Krankenhaus Wien, Dept. Gynecology and Obstetrics, Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Reinthaller
authors.affiliation: All-Ireland Co-operative Oncology Group, Dublin, Ireland.
authors.forename: Paula
authors.initials: P
authors.lastname: Calvert
authors.affiliation: University of Cincinnati Cancer Institute, Cincinnati, OH, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Herzog
authors.affiliation: Evangelisches Krankenhaus Düsseldorf, Düsseldorf, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Meier
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jae-Weon
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Vall d'Hebron University Hospital, Dept. of Medical Oncology, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: del Campo
authors.affiliation: The Prince of Wales Cancer Center, Dept. of Medical Oncology, Randwick, NSW, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Friedlander
authors.affiliation: Department of Uro-gynecologic Oncology, Istituto Nazionale Tumori Fondazione G Pascale-IRCCS, Naples, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Pisano
authors.affiliation: Department of Obstetrics and Gynecology, Jikei University School of Medicine, Daisan Hospital, Tokyo, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Isonishi
authors.affiliation: GlaxoSmithKline, Collegeville, PA, USA.
authors.forename: Rocco J
authors.initials: RJ
authors.lastname: Crescenzo
authors.affiliation: GlaxoSmithKline Pharmaceuticals, Uxbridge, United Kingdom.
authors.forename: Catherine
authors.initials: C
authors.lastname: Barrett
authors.affiliation: GlaxoSmithKline, Collegeville, PA, USA.
authors.forename: Karrie
authors.initials: K
authors.lastname: Wang
authors.affiliation: GlaxoSmithKline, Collegeville, PA, USA.
authors.forename: Ionel
authors.initials: I
authors.lastname: Mitrica
authors.affiliation: Department of Gynecology and Gynecologic Oncology, Kliniken Essen Mitte, Essen, Germany. Electronic address: prof.dubois@googlemail.com.
authors.forename: Andreas
authors.initials: A
authors.lastname: du Bois
mesh_terms: D020533:Angiogenesis Inhibitors; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D004311:Double-Blind Method; D023381:Endpoint Determination / Q000379:methods / Q000592:standards; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D005260:Female; D006801:Humans; D007191:Indazoles; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D011743:Pyrimidines / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib
keywords: Disease progression; Independent central review; Ovarian cancer; Progression-free survival