title: Phase II, randomized trial to compare anastrozole combined with gefitinib or placebo in postmenopausal women with hormone receptor-positive metastatic breast cancer.
abstract: OBJECTIVE
  This phase II randomized trial evaluated the efficacy and tolerability of anastrozole combined with gefitinib or anastrozole with placebo in women with hormone receptor-positive metastatic breast cancer (MBC).
  
  
  METHODS
  Postmenopausal women with hormone receptor-positive measurable or evaluable MBC who had not received prior endocrine therapy for this disease stage or who developed metastatic disease during/after adjuvant tamoxifen were eligible. The primary response variable was progression-free survival (PFS) and secondary response variables included clinical benefit rate, objective response rate, overall survival, safety and tolerability, and pharmacokinetics. Tumor biomarker evaluation was an exploratory objective.
  
  
  RESULTS
  Forty-three patients were randomized to anastrozole plus gefitinib and 50 patients were randomized to anastrozole plus placebo of a planned total of 174 patients (enrollment was prematurely discontinued due to slow recruitment). PFS for patients receiving the combination of anastrozole and gefitinib was longer than for patients receiving anastrozole plus placebo [hazard ratio (gefitinib/placebo), 0.55; 95% confidence interval, 0.32-0.94; median PFS, 14.7 versus 8.4 months]. The clinical benefit rate was 49% versus 34%, and the objective response rate was 2% versus 12% with anastrozole plus gefitinib and anastrozole plus placebo, respectively. No evidence of interaction between baseline biomarker levels and relative treatment effect was found. No unexpected adverse events were observed.
  
  
  CONCLUSIONS
  This small randomized study showed that anastrozole in combination with gefitinib is associated with a marked advantage in PFS compared with anastrozole plus placebo, and that the combination was tolerated in postmenopausal women with hormone receptor-positive MBC. Further investigation of epidermal growth factor receptor inhibition in combination with endocrine therapy may be warranted.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030-1439, USA. mcristof@mdanderson.org
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Aroop
authors.initials: A
authors.lastname: Mangalik
authors.forename: Melanie
authors.initials: M
authors.lastname: Royce
authors.forename: Ian
authors.initials: I
authors.lastname: Rabinowitz
authors.forename: Francis P
authors.initials: FP
authors.lastname: Arena
authors.forename: Joan F
authors.initials: JF
authors.lastname: Kroener
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Curcio
authors.forename: Claire
authors.initials: C
authors.lastname: Watkins
authors.forename: Sarah
authors.initials: S
authors.lastname: Bacus
authors.forename: Elsa M
authors.initials: EM
authors.lastname: Cora
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Anderson
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Magill
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004311:Double-Blind Method; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009570:Nitriles / Q000008:administration & dosage; D017698:Postmenopause; D011446:Prospective Studies; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D015996:Survival Rate; D014018:Tissue Distribution; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage
chemical_list: D000077384:Anastrozole; D066246:ErbB Receptors; D000077156:Gefitinib; D009570:Nitriles; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles; C512478:EGFR protein, human; C508053:ERBB2 protein, human