title: Efficacy of pemetrexed as second-line therapy in advanced NSCLC after either treatment-free interval or maintenance therapy with gemcitabine or erlotinib in IFCT-GFPC 05-02 phase III study.
abstract: BACKGROUND
  Maintenance therapy in advanced non-small-cell lung cancer (NSCLC) might lead to resistance to subsequent treatments. IFCT-GFPC 0502 study showed a progression-free survival (PFS) benefit with gemcitabine or erlotinib maintenance compared with observation after cisplatin-gemcitabine chemotherapy. The trial included a pre-defined pemetrexed second-line therapy, allowing post-hoc assessment of its efficacy according to previous maintenance treatment or treatment-free interval.
  
  
  METHODS
  Stage IIIB/IV NSCLC patients were randomized after four cycles of cisplatin-gemcitabine chemotherapy to either observation or to receive maintenance therapy with gemcitabine or erlotinib. Pemetrexed was given as second-line treatment on disease progression in all arms. PFS and overall survival (OS) were assessed from the beginning of pemetrexed therapy according to randomization arm.
  
  
  RESULTS
  Of the 464 randomized patients, 360 (78 %) received second-line pemetrexed (130 [84%], 114 [74%], and 116 [75%] in observation, gemcitabine, and erlotinib arm, respectively). Median number of pemetrexed cycles was 3 (1-40) in all arms. Median PFS did not differ between gemcitabine and observation arms (4.2 versus 3.9 months, hazard ratio [HR] [95% confidence interval [CI] 0.81 [0.62-1.06]) or between erlotinib and observation arms (4.2 versus 3.9 months, HR 0.83 [0.64-1.09]). OS data showed a non-significant improvement with gemcitabine arm versus observation arm (8.3 versus 7.5 months, HR 0.81 [0.61-1.07]) or erlotinib arm versus observation arm (9.1 versus 7.5 months, HR 0.80 [0.61-1.05]). Results were similar for non-squamous patients. Grade 3 to 4 treatment-related adverse events (AEs) were comparable in all arms.
  
  
  CONCLUSIONS
  Maintenance therapy with gemcitabine continuation or erlotinib does not seem to impair efficacy of second-line pemetrexed comparatively to administration after a treatment-free interval.
authors.affiliation: Hospices Civils de Lyon, Lyon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bylicki
authors.forename: Céline
authors.initials: C
authors.lastname: Ferlay
authors.forename: Christos
authors.initials: C
authors.lastname: Chouaid
authors.forename: Armelle
authors.initials: A
authors.lastname: Lavolé
authors.forename: Fabrice
authors.initials: F
authors.lastname: Barlési
authors.forename: Cathérine
authors.initials: C
authors.lastname: Dubos
authors.forename: Virginie
authors.initials: V
authors.lastname: Westeel
authors.forename: Jacky
authors.initials: J
authors.lastname: Créquit
authors.forename: Roman
authors.initials: R
authors.lastname: Corre
authors.forename: Alain
authors.initials: A
authors.lastname: Vergnenègre
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: Fabien
authors.initials: F
authors.lastname: Vaylet
authors.forename: Lionel
authors.initials: L
authors.lastname: Falchero
authors.forename: Michel
authors.initials: M
authors.lastname: Poudenx
authors.forename: Pauline
authors.initials: P
authors.lastname: Linard
authors.forename: David
authors.initials: D
authors.lastname: Pérol
authors.forename: Gérald
authors.initials: G
authors.lastname: Zalcman
authors.forename: Maurice
authors.initials: M
authors.lastname: Pérol
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069347:Erlotinib Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage; D016879:Salvage Therapy; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D005971:Glutamates; D011799:Quinazolines; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000069347:Erlotinib Hydrochloride; D000093542:Gemcitabine