title: Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers.
abstract: OBJECTIVE
  Epidermal growth factor receptor (EGFR) mutations have been found in the majority of gefitinib-responsive non-small cell lung cancer (NSCLC) patients from retrospective studies. We sought to compile the available phase II and prospective trials of this EGFR tyrosine kinase inhibitor (TKI) to better understand the efficacy and safety of selecting patients to receive gefitinib based on their genotype.
  
  
  METHODS
  We searched published trials involving EGFR-mutant patients and gefitinib. Five reports were identified (published between June 2006 and April 2007) in which gefitinib was given in a prospective manner to EGFR mutation positive patients at a dose of 250mg/day. Responses were determined by RECIST and toxicities by NCI-CTC.
  
  
  RESULTS
  A total of 101 patients were pooled from these studies. Fifty-nine received gefitinib as their first line of therapy and 42 after having received chemotherapy. The combined rate of complete and partial response (CR+PR) in the 99 measured patients was 80.8% (80/99) and only 7.1% (7/99) had progressive disease as best response. The response rate (CR+PR) for exon 19 deletion and L858R patients were 80.3% (53/66) and 81.8% (27/33), respectively. The median progression-free survival ranged from 7.7 to 12.9 months. Overall survival had not been reached in 4/5 reports and was 15.4 months in one of them. Gefitinib administration was safe (<50% of patients developed grades 1-2 skin rash or diarrhea) and interstitial lung disease was only reported in two patients (2%), without deaths.
  
  
  CONCLUSIONS
  Gefitinib monotherapy leads to objective responses in most patients with EGFR mutations. Both L858R and deletion 19 mutations derived similar clinical benefits. Small molecule TKIs are the new treatment paradigm for EGFR-mutant NSCLC.
authors.affiliation: Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Av., Rabb 430, Boston, MA 02215, USA. dbcosta@bismc.harvard.edu
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Costa
authors.forename: Susumu
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Tenen
authors.forename: Mark S
authors.initials: MS
authors.lastname: Huberman
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000819:agonists; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D017322:Clinical Trials, Phase II as Topic; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000077156:Gefitinib; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D009154:Mutation; D009367:Neoplasm Staging; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib