title: Prediction of survival benefits from progression-free survival benefits in advanced non-small-cell lung cancer: evidence from a meta-analysis of 2334 patients from 5 randomised trials.
abstract: OBJECTIVE
  To investigate whether progression-free survival (PFS) can be considered a surrogate endpoint for overall survival (OS) in advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Meta-analysis of individual patient data from randomised trials.
  
  
  METHODS
  Five randomised controlled trials comparing docetaxel-based chemotherapy with vinorelbine-based chemotherapy for the first-line treatment of NSCLC.
  
  
  METHODS
  2331 patients with advanced NSCLC.
  
  
  METHODS
  Surrogacy of PFS for OS was assessed through the association between these endpoints and between the treatment effects on these endpoints. The surrogate threshold effect was the minimum treatment effect on PFS required to predict a non-zero treatment effect on OS.
  
  
  RESULTS
  The median follow-up of patients still alive was 23.4 months. Median OS was 10 months and median PFS was 5.5 months. The treatment effects on PFS and OS were correlated, whether using centres (R&sup2;=0.62, 95% CI 0.52 to 0.72) or prognostic strata (R&sup2;=0.72, 95% CI 0.60 to 0.84) as units of analysis. The surrogate threshold effect was a PFS hazard ratio (HR) of 0.49 using centres or 0.53 using prognostic strata.
  
  
  CONCLUSIONS
  These analyses provide only modest support for considering PFS as an acceptable surrogate for OS in patients with advanced NSCLC. Only treatments that have a major impact on PFS (risk reduction of at least 50%) would be expected to also have a significant effect on OS. Whether these results also apply to targeted therapies is an open question that requires independent evaluation.
authors.affiliation: Université Jean Monnet, Saint-Etienne, France.
authors.forename: Silvy
authors.initials: S
authors.lastname: Laporte
authors.forename: Pierre
authors.initials: P
authors.lastname: Squifflet
authors.forename: Noémie
authors.initials: N
authors.lastname: Baroux
authors.forename: Frank
authors.initials: F
authors.lastname: Fossella
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pujol
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douillard
authors.forename: Shinzohy
authors.initials: S
authors.lastname: Kudoh
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pignon
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Quinaux
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse