title: Randomized phase III study of erlotinib versus observation in patients with no evidence of disease progression after first-line platin-based chemotherapy for ovarian carcinoma: a European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group, and Gynecologic Cancer Intergroup study.
abstract: OBJECTIVE
  This trial evaluated the efficacy of maintenance erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, after first-line chemotherapy.
  
  
  METHODS
  Eligible patients had high-risk International Federation of Gynecology and Obstetrics stage I or stage II to IV epithelial ovarian, primary peritoneal, or fallopian tube cancer and were not selected for EGFR expression. All patients underwent first-line platinum-based chemotherapy (CT) and showed no signs of progression at the end of CT. Patients were randomly assigned to maintenance erlotinib 150 mg orally daily for 2 years or to observation. EGFR immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and mutation analyses were performed in 318 patients.
  
  
  RESULTS
  Between October 2005 and February 2008, 835 patients were randomly assigned (median follow-up, 51 months). Twenty-six percent of the patients stopped erlotinib as a result of adverse effects (of these, 67% were due to rash). For erlotinib and observation, respectively, the median progression-free survival was 12.7 and 12.4 months (hazard ratio [HR], 1.05; 95% CI, 0.90 to 1.23), and the median overall survival was 50.8 and 59.1 months (HR, 0.99; 95% CI, 0.81 to 1.20 months), respectively. No subgroup could be identified with improved effect of erlotinib, based on IHC or FISH for EGFR, or mutations in genes related to the EGFR pathway, or on rash during erlotinib therapy. However, patients with a positive FISH EGFR score had a worse overall survival (46.1 months) than those with a negative score (67.0 months; HR, 1.56; 95% CI, 1.01 to 2.40; P = .044). Global health/quality-of-life scores showed a significant difference during the first year (P = .0102) in favor of the observation arm.
  
  
  CONCLUSIONS
  Maintenance erlotinib after first-line treatment in ovarian cancer did not improve progression-free or overall survival.
authors.affiliation: Ignace B. Vergote and Evelyn Despierre, University Hospitals Leuven and Katholieke Universiteit Leuven, Leuven; Corneel Coens, European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium; Antonio Jimeno, University of Colorado School of Medicine, Aurora, CO; Florence Joly, Centre François Baclesse Caen, Caen; Anne Lesoin, Centre Oscar Lambret, Lille; Isabelle Ray-Coquard, Centre Léon Bérard, Lyon; Laure Favier, Centre Georges François Leclerc, Dijon; Hervé Curé, Unicancer Institut Jean Godinot, Reims; Eric Pujade-Lauraine, Hôpital Hôtel-Dieu, Paris, France; Dionyssios Katsaros, University of Turin; Annamaria Ferrero, Ospedale Mauriziano Umberto I, Turin; Nicoletta Colombo, University of Milan-Bicocca and Istituto Europeo di Oncologia, Milan, Italy; Christian Marth, Medical University of Innsbruck, Innsbruck; Alexander Reinthaller, Medical University of Vienna, Vienna, Austria; Marcia Hall, Mount Vernon Cancer Centre, Middlesex; John Green, University of Liverpool, Liverpool; Nick Simon Reed, Gartnavel General Hospitals, Glasgow, United Kingdom; Christopher B. Steer, Border Medical Oncology, Wodonga; Martin Buck, Government of Western Australia, Department of Health, Perth, Australia; and Antonio Casado, Universitario San Carlos, Madrid, Spain.
authors.forename: Ignace B
authors.initials: IB
authors.lastname: Vergote
authors.forename: Antonio
authors.initials: A
authors.lastname: Jimeno
authors.forename: Florence
authors.initials: F
authors.lastname: Joly
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Katsaros
authors.forename: Corneel
authors.initials: C
authors.lastname: Coens
authors.forename: Evelyn
authors.initials: E
authors.lastname: Despierre
authors.forename: Christian
authors.initials: C
authors.lastname: Marth
authors.forename: Marcia
authors.initials: M
authors.lastname: Hall
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Steer
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Colombo
authors.forename: Anne
authors.initials: A
authors.lastname: Lesoin
authors.forename: Antonio
authors.initials: A
authors.lastname: Casado
authors.forename: Alexander
authors.initials: A
authors.lastname: Reinthaller
authors.forename: John
authors.initials: J
authors.lastname: Green
authors.forename: Martin
authors.initials: M
authors.lastname: Buck
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ray-Coquard
authors.forename: Annamaria
authors.initials: A
authors.lastname: Ferrero
authors.forename: Laure
authors.initials: L
authors.lastname: Favier
authors.forename: Nick Simon
authors.initials: NS
authors.lastname: Reed
authors.forename: Hervé
authors.initials: H
authors.lastname: Curé
authors.forename: Eric
authors.initials: E
authors.lastname: Pujade-Lauraine
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D003875:Drug Eruptions / Q000209:etiology; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005060:Europe; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D060046:Maintenance Chemotherapy; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017671:Platinum Compounds / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011788:Quality of Life; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D015398:Signal Transduction / Q000235:genetics; D057832:Watchful Waiting
chemical_list: D017671:Platinum Compounds; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors