title: Meta-analysis of single-agent chemotherapy compared with combination chemotherapy as second-line treatment of advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  Doublet chemotherapy is more effective than single-agent as first-line treatment of advanced non-small-cell lung cancer (NSCLC). As second-line treatment, several randomized trials have been performed comparing single-agent with doublet chemotherapy, but each trial had an insufficient power to detect potentially relevant differences in survival.
  
  
  METHODS
  We performed meta-analysis of individual patient data from randomized trials, both published and unpublished, comparing single-agent with doublet chemotherapy as second-line treatment of advanced NSCLC. Primary end point was overall survival (OS). All statistical analyses were stratified by trial.
  
  
  RESULTS
  Eight eligible trials were identified. Data of two trials were not available, and data of six trials (847 patients) were collected. Median age was 61 years. Performance status was 0 or 1 in 90%; 80% of patients had received previous platin-based chemotherapy. OS was not significantly different between arms (P = .32). Median OS was 37.3 and 34.7 weeks in the doublet and single-agent arms, respectively. Hazard ratio (HR) was 0.92 (95% CI, 0.79 to 1.08). Response rate was 15.1% with doublet and 7.3% with single-agent (P = .0004). Median progression-free survival was 14 weeks for doublet and 11.7 weeks for single agent (P = .0009; HR, 0.79; 95% CI, 0.68 to 0.91). There was no significant heterogeneity among trials for the three efficacy outcomes. Patients treated with doublet chemotherapy had significantly more grade 3 to 4 hematologic (41% v 25%; P < .0001) and grade 3 to 4 nonhematologic toxicity (28% v 22%; P = .034).
  
  
  CONCLUSIONS
  Doublet chemotherapy as second-line treatment of advanced NSCLC significantly increases response rate and progression-free survival, but is more toxic and does not improve overall survival compared to single-agent.
authors.affiliation: Clinical Trials Unit, National Cancer Institute, Department of Medicine and Public Health, Second University of Napoli, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Maio
authors.forename: Paolo
authors.initials: P
authors.lastname: Chiodini
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
authors.forename: Dora
authors.initials: D
authors.lastname: Hatzidaki
authors.forename: Koji
authors.initials: K
authors.lastname: Takeda
authors.forename: Floris M
authors.initials: FM
authors.lastname: Wachters
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gebbia
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morabito
authors.forename: Ciro
authors.initials: C
authors.lastname: Gallo
authors.forename: Francesco
authors.initials: F
authors.lastname: Perrone
authors.forename: Cesare
authors.initials: C
authors.lastname: Gridelli
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents