title: Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  This phase III study investigated whether continuation maintenance with gemcitabine or switch maintenance with erlotinib improves clinical outcome compared with observation in patients with advanced non-small-cell lung cancer (NSCLC) whose disease was controlled after cisplatin-gemcitabine induction chemotherapy.
  
  
  METHODS
  Four hundred sixty-four patients with stage IIIB/IV NSCLC without tumor progression after four cycles of cisplatin-gemcitabine were randomly assigned to observation or to gemcitabine (1,250 mg/m(2) days 1 and 8 of a 3-week cycle) or daily erlotinib (150 mg/day) study arms. On disease progression, patients in all three arms received pemetrexed (500 mg/m(2) once every 21 days) as predefined second-line therapy. The primary end point was progression-free survival (PFS).
  
  
  RESULTS
  PFS was significantly prolonged by gemcitabine (median, 3.8 v 1.9 months; hazard ratio [HR], 0.56; 95% CI, 0.44 to 0.72; log-rank P < .001) and erlotinib (median, 2.9 v 1.9 months; HR, 0.69; 95% CI, 0.54 to 0.88; log-rank P = .003) versus observation; this benefit was consistent across all clinical subgroups. Both maintenance strategies resulted in a nonsignificant improvement in overall survival (OS); patients who received second-line pemetrexed or with a performance status of 0 appeared to derive greater benefit. Exploratory analysis showed that magnitude of response to induction chemotherapy may affect the OS benefit as a result of gemcitabine maintenance. Maintenance gemcitabine and erlotinib were well tolerated with no unexpected adverse events.
  
  
  CONCLUSIONS
  Gemcitabine continuation maintenance or erlotinib switch maintenance significantly reduces disease progression in patients with advanced NSCLC treated with cisplatin-gemcitabine as first-line chemotherapy. Response to induction chemotherapy may affect OS only for continuation maintenance.
authors.affiliation: Hospices Civils de Lyon, Lyon Cedex 08, France. maurice.perol@lyon.unicancer.fr
authors.forename: Maurice
authors.initials: M
authors.lastname: Pérol
authors.forename: Christos
authors.initials: C
authors.lastname: Chouaid
authors.forename: David
authors.initials: D
authors.lastname: Pérol
authors.forename: Fabrice
authors.initials: F
authors.lastname: Barlési
authors.forename: Radj
authors.initials: R
authors.lastname: Gervais
authors.forename: Virginie
authors.initials: V
authors.lastname: Westeel
authors.forename: Jacky
authors.initials: J
authors.lastname: Crequit
authors.forename: Hervé
authors.initials: H
authors.lastname: Léna
authors.forename: Alain
authors.initials: A
authors.lastname: Vergnenègre
authors.forename: Gérard
authors.initials: G
authors.lastname: Zalcman
authors.forename: Isabelle
authors.initials: I
authors.lastname: Monnet
authors.forename: Hervé
authors.initials: H
authors.lastname: Le Caer
authors.forename: Pierre
authors.initials: P
authors.lastname: Fournel
authors.forename: Lionel
authors.initials: L
authors.lastname: Falchero
authors.forename: Michel
authors.initials: M
authors.lastname: Poudenx
authors.forename: Fabien
authors.initials: F
authors.lastname: Vaylet
authors.forename: Céline
authors.initials: C
authors.lastname: Ségura-Ferlay
authors.forename: Mojgan
authors.initials: M
authors.lastname: Devouassoux-Shisheboran
authors.forename: Miquel
authors.initials: M
authors.lastname: Taron
authors.forename: Bernard
authors.initials: B
authors.lastname: Milleron
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D008175:Lung Neoplasms / Q000188:drug therapy*; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage* / Q000627:therapeutic use; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D003841:Deoxycytidine; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D002945:Cisplatin; D000093542:Gemcitabine