title: Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer.
abstract: OBJECTIVE
  To test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity.
  
  
  METHODS
  Forty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed by consolidation paclitaxel-carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status.
  
  
  RESULTS
  Of 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown).
  
  
  CONCLUSIONS
  Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of distant failures underscores the need for effective systemic therapy.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: rkomaki@mdanderson.org.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Pamela K
authors.initials: PK
authors.lastname: Allen
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Xiong
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: George R
authors.initials: GR
authors.lastname: Blumenschein
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ximing
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: James W
authors.initials: JW
authors.lastname: Welsh
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.affiliation: Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Diane D
authors.initials: DD
authors.lastname: Liu
authors.affiliation: Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Waun Ki
authors.initials: WK
authors.lastname: Hong
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000556:secondary / Q000628:therapy; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019540:Area Under Curve; D001932:Brain Neoplasms / Q000556:secondary; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000556:secondary / Q000628:therapy; D059248:Chemoradiotherapy / Q000379:methods*; D018450:Disease Progression; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017239:Paclitaxel / Q000008:administration & dosage; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D050397:Radiotherapy, Intensity-Modulated; D013997:Time Factors
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D016190:Carboplatin; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D017239:Paclitaxel