title: A European Organisation for Research and Treatment of Cancer randomized, double-blind, placebo-controlled, multicentre phase II trial of anastrozole in combination with gefitinib or placebo in hormone receptor-positive advanced breast cancer (NCT00066378).
abstract: BACKGROUND
  Preclinical data suggest that epidermal growth factor receptor (EGFR) inhibitors (e.g. gefitinib) can delay endocrine resistance in breast cancer. A double-blind, placebo-controlled, phase II trial investigated whether adding gefitinib (G) to anastrozole (A) would improve outcome in advanced breast cancer (ABC).
  
  
  METHODS
  Postmenopausal pre-treated hormone receptor-positive ABC patients (locally recurrent or metastatic) were 1:1 randomized to A (1 mg/d) plus G 250 mg/d or plus placebo (P). Patients who had prior treatment with an aromatase inhibitor in metastatic setting or with trastuzumab, anti-EGFR or anti-VEGF agents were excluded. Treatment was given until disease progression, unacceptable toxicity or patient withdrawal. Progression-free survival (PFS) rate at 1 year was assessed according to Response Evaluation Criteria in Solid Tumours, version 1.0.
  
  
  RESULTS
  Of 108 planned patients, 71 were recruited (36 in A/G and 35 in A/P). The trial closed prematurely due to slow recruitment; 31 patients had prior chemotherapy and 53 prior endocrine therapy (all except one received tamoxifen); 60% in adjuvant and 16% in metastatic setting received tamoxifen; 59 patients had visceral disease. Median follow-up was 18 months. PFS rate at 1 year was 35% for A/G and 32% for A/P arm. Objective responses were six (22%) in the A/G and nine (28%) in the A/P arm. Median duration of response was 13.8 and 18.6 months in the A/G and A/P arms, respectively. Fatigue (35%), diarrhoea (31%), rash (32%), dry skin (27%), and arthralgia/myalgia (27%) were the commonest adverse events in the A/G arm.
  
  
  CONCLUSIONS
  This phase II study, although prematurely closed, did not show a signal that adding G to A improves PFS at 1 year and its use is not supported. Gastrointestinal and skin toxicities were more pronounced with G resulting in premature therapy interruption in almost 1 in 3 patients (ClinicalTrials.gov number, NCT00066378).
authors.affiliation: EORTC-Headquarters, Medical Department, Brussels, Belgium. Electronic address: konstantinos.tryfonidis@eortc.be.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tryfonidis
authors.affiliation: Acıbadem Üniversitesi İç Hastalıkları/Tıbbi Onkoloji, Turkey. Electronic address: gabasaran@gmail.com.
authors.forename: Gul
authors.initials: G
authors.lastname: Basaran
authors.affiliation: EORTC-Headquarters, Statistical Department, Belgium. Electronic address: jan.bogaerts@eortc.be.
authors.forename: Jan
authors.initials: J
authors.lastname: Bogaerts
authors.affiliation: Institute Bergonie, Bordeaux, France. Electronic address: M.Debled@bordeaux.unicancer.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Debled
authors.affiliation: GZA Sint Augustinus, Antwerp, Belgium. Electronic address: Luc.dirix@telenet.be.
authors.forename: Luc
authors.initials: L
authors.lastname: Dirix
authors.affiliation: Ctr Becquerel-Rouen, France. Electronic address: jean-christophe.thery@chb.unicancer.fr.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Thery
authors.affiliation: Radboudumc Nijmegen/Maastricht UMC+, Netherlands. Electronic address: vcg.tjan.heijnen@mumc.nl.
authors.forename: Vivianne C G
authors.initials: VC
authors.lastname: Tjan-Heijnen
authors.affiliation: ZNA Middelheim, Belgium. Electronic address: Danielle.VandenWeyngaert@zna.be.
authors.forename: Danielle
authors.initials: D
authors.lastname: Van den Weyngaert
authors.affiliation: University Clinic Golnik, Slovenia. Electronic address: Tanja.Cufer@klinika-golnik.si.
authors.forename: Tanja
authors.initials: T
authors.lastname: Cufer
authors.affiliation: Institute Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium. Electronic address: martine.piccart@bordet.be.
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart
authors.affiliation: NHS-Lothian, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: D.Cameron@ed.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Cameron
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004311:Double-Blind Method; D057239:Early Termination of Clinical Trials; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage
chemical_list: D000077384:Anastrozole; D000077156:Gefitinib; D009570:Nitriles; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles; C508053:ERBB2 protein, human
keywords: Anastrozole; Endocrine resistance; Gefitinib; Metastatic breast cancer