title: Chemoradiotherapy and gefitinib in stage III non-small cell lung cancer with epidermal growth factor receptor and KRAS mutation analysis: cancer and leukemia group B (CALEB) 30106, a CALGB-stratified phase II trial.
abstract: BACKGROUND
  This study evaluated the addition of gefitinib to sequential or concurrent chemoradiotherapy (CRT) in unresectable stage III non-small cell lung cancer.
  
  
  METHODS
  Between May 2002 and April 2005, 63 patients were entered before the study closing early. All received two cycles paclitaxel 200 mg/m and carboplatin area under the curve 6 intravenous plus gefitinib 250 mg daily. Poor risk stratum 1 (> or =5% weight loss and/or performance status 2) received radiotherapy 200 cGy for 33 fractions (6600 cGy) and gefitinib 250 mg daily. Good-risk stratum 2 (performance status: 0-1 weight loss and <5%) received the same RT with gefitinib 250 mg daily and weekly paclitaxel 50 mg/m plus carboplatin AUC 2. Consolidation gefitinib until progression was started after all toxicities were grade < or =2.
  
  
  RESULTS
  Acute high-grade infield toxicities were not clearly increased compared with historical CRT data. Poor-risk (N = 21) median progression-free survival was 13.4 months (95% confidence interval [CI]: 6.4-25.2) and median overall survival 19.0 months (95% CI: 9.9-28.4). Good-risk (N = 39) median progression-free survival was 9.2 months (95% CI: 6.7-12.2), and median overall survival was 13 months (95% CI: 8.5-17.2). Thirteen of 45 tumors analyzed had activating epidermal growth factor receptor (EGFR) mutations, and 2 of 13 also had T790M mutations. Seven tumors of 45 had KRAS mutations. There was no apparent survival difference with EGFR-activating mutations versus wild type or KRAS mutation versus wild type.
  
  
  CONCLUSIONS
  Survival of poor-risk patients with wild type or mutated EGFR receiving sequential CRT with gefitinib was promising. Survival for good-risk patients receiving concurrent CRT plus gefitinib was disappointing even for tumors with activating EGFR mutations.
authors.affiliation: Division of Medical Oncology, Duke University Medical Center, Durham, NC 27710, USA. ready001@mc.duke.edu
authors.forename: Neal
authors.initials: N
authors.lastname: Ready
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bogart
authors.forename: Thomas
authors.initials: T
authors.lastname: Dipetrillo
authors.forename: Jennifer
authors.initials: J
authors.lastname: Garst
authors.forename: Stephen
authors.initials: S
authors.lastname: Graziano
authors.forename: Lin
authors.initials: L
authors.lastname: Gu
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.forename: Mark R
authors.initials: MR
authors.lastname: Green
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000473:pathology / Q000628:therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines / Q000008:administration & dosage; D011878:Radiotherapy; D015996:Survival Rate; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D016190:Carboplatin; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D017239:Paclitaxel; D000077156:Gefitinib