title: Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial.
abstract: BACKGROUND
  Erlotinib is registered for treatment of all patients with advanced non-small-cell lung cancer (NSCLC). However, its efficacy for treatment of patients whose tumours are EGFR wild-type-which includes most patients-is still contentious. We assessed the efficacy of erlotinib compared with a standard second-line chemotherapy in such patients.
  
  
  METHODS
  We did this randomised controlled trial in 52 Italian hospitals. We enrolled patients who had metastatic NSCLC, had had platinum-based chemotherapy, and had wild-type EGFR as assessed by direct sequencing. Patients were randomly assigned centrally (1:1) to receive either erlotinib orally 150 mg/day or docetaxel intravenously 75 mg/m(2) every 21 days or 35 mg/m(2) on days 1, 8, and 15, every 28 days. Randomisation was stratified by centre, stage, type of first-line chemotherapy, and performance status. Patients and investigators who gave treatments or assessed outcomes were not masked to treatment allocation, investigators who analysed results were. The primary endpoint was overall survival in the intention-to-treat population. The study is registered at ClinicalTrials.gov, number NCT00637910.
  
  
  RESULTS
  We screened 702 patients, of whom we genotyped 540. 222 patients were enrolled (110 assigned to docetaxel vs 112 assigned to erlotinib). Median overall survival was 8·2 months (95% CI 5·8-10·9) with docetaxel versus 5·4 months (4·5-6·8) with erlotinib (adjusted hazard ratio [HR] 0·73, 95% CI 0·53-1·00; p=0·05). Progression-free survival was significantly better with docetaxel than with erlotinib: median progression-free survival was 2·9 months (95% CI 2·4-3·8) with docetaxel versus 2·4 months (2·1-2·6) with erlotinib (adjusted HR 0·71, 95% CI 0·53-0·95; p=0·02). The most common grade 3-4 toxic effects were: low absolute neutrophil count (21 [20%] of 104 in the docetaxel group vs none of 107 in the erlotinib group), skin toxic effects (none vs 15 [14%]), and asthenia (ten [10%] vs six [6%]).
  
  
  CONCLUSIONS
  Our results show that chemotherapy is more effective than erlotinib for second-line treatment for previously treated patients with NSCLC who have wild-type EGFR tumours.
authors.affiliation: Department of Medical Oncology, Fatebenefratelli e Oftalmico Hospital, Milan, Italy.j.stebbing@imperial.ac.uk
authors.forename: Marina Chiara
authors.initials: MC
authors.lastname: Garassino
authors.forename: Olga
authors.initials: O
authors.lastname: Martelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Broggini
authors.forename: Gabriella
authors.initials: G
authors.lastname: Farina
authors.forename: Silvio
authors.initials: S
authors.lastname: Veronese
authors.forename: Eliana
authors.initials: E
authors.lastname: Rulli
authors.forename: Filippo
authors.initials: F
authors.lastname: Bianchi
authors.forename: Anna
authors.initials: A
authors.lastname: Bettini
authors.forename: Flavia
authors.initials: F
authors.lastname: Longo
authors.forename: Luca
authors.initials: L
authors.lastname: Moscetti
authors.forename: Maurizio
authors.initials: M
authors.lastname: Tomirotti
authors.forename: Mirko
authors.initials: M
authors.lastname: Marabese
authors.forename: Monica
authors.initials: M
authors.lastname: Ganzinelli
authors.forename: Calogero
authors.initials: C
authors.lastname: Lauricella
authors.forename: Roberto
authors.initials: R
authors.lastname: Labianca
authors.forename: Irene
authors.initials: I
authors.lastname: Floriani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giaccone
authors.forename: Valter
authors.initials: V
authors.lastname: Torri
authors.forename: Alberto
authors.initials: A
authors.lastname: Scanni
authors.forename: Silvia
authors.initials: S
authors.lastname: Marsoni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D000077143:Docetaxel; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines / Q000627:therapeutic use*; D043823:Taxoids / Q000627:therapeutic use*; D018631:ras Proteins / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D043823:Taxoids; D000077143:Docetaxel; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins