title: Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced non-small-cell lung cancer: results of the GOIRC 02-2006 randomized phase II study and pooled analysis with the NVALT7 trial.
abstract: OBJECTIVE
  To compare efficacy of pemetrexed versus pemetrexed plus carboplatin in pretreated patients with advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Patients with advanced NSCLC, in progression during or after first-line platinum-based chemotherapy, were randomly assigned to receive pemetrexed (arm A) or pemetrexed plus carboplatin (arm B). Primary end point was progression-free survival (PFS). A preplanned pooled analysis of the results of this study with those of the NVALT7 study was carried out to assess the impact of carboplatin added to pemetrexed in terms of overall survival (OS).
  
  
  RESULTS
  From July 2007 to October 2009, 239 patients (arm A, n = 120; arm B, n = 119) were enrolled. Median PFS was 3.6 months for arm A versus 3.5 months for arm B (hazard ratio [HR], 1.05; 95% CI, 0.81 to 1.36; P = .706). No statistically significant differences in response rate, OS, or toxicity were observed. A total of 479 patients were included in the pooled analysis. OS was not improved by the addition of carboplatin to pemetrexed (HR, 90; 95% CI, 0.74 to 1.10; P = .316; P heterogeneity = .495). In the subgroup analyses, the addition of carboplatin to pemetrexed in patients with squamous tumors led to a statistically significant improvement in OS from 5.4 to 9 months (adjusted HR, 0.58; 95% CI, 0.37 to 0.91; P interaction test = .039).
  
  
  CONCLUSIONS
  Second-line treatment of advanced NSCLC with pemetrexed plus carboplatin does not improve survival outcomes as compared with single-agent pemetrexed. The benefit observed with carboplatin addition in squamous tumors may warrant further investigation.
authors.affiliation: Azienda Ospedaliero-Universitaria, Parma, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ardizzoni
authors.forename: Marcello
authors.initials: M
authors.lastname: Tiseo
authors.forename: Luca
authors.initials: L
authors.lastname: Boni
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Vincent
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Passalacqua
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Buti
authors.forename: Domenico
authors.initials: D
authors.lastname: Amoroso
authors.forename: Andrea
authors.initials: A
authors.lastname: Camerini
authors.forename: Roberto
authors.initials: R
authors.lastname: Labianca
authors.forename: Giovenzio
authors.initials: G
authors.lastname: Genestreti
authors.forename: Corrado
authors.initials: C
authors.lastname: Boni
authors.forename: Libero
authors.initials: L
authors.lastname: Ciuffreda
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Costanzo
authors.forename: Filippo
authors.initials: F
authors.lastname: de Marinis
authors.forename: Lucio
authors.initials: L
authors.lastname: Crinò
authors.forename: Antonio
authors.initials: A
authors.lastname: Santo
authors.forename: Antonio
authors.initials: A
authors.lastname: Pazzola
authors.forename: Fausto
authors.initials: F
authors.lastname: Barbieri
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Zilembo
authors.forename: Ida
authors.initials: I
authors.lastname: Colantonio
authors.forename: Carmelo
authors.initials: C
authors.lastname: Tibaldi
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Mattioli
authors.forename: Mara A
authors.initials: MA
authors.lastname: Cafferata
authors.forename: Roberta
authors.initials: R
authors.lastname: Camisa
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D016190:Carboplatin