title: Progression-free survival as a potential surrogate for overall survival in metastatic breast cancer.
abstract: BACKGROUND
  Progression-free survival (PFS) and time to progression (TTP) are frequently used to establish the clinical efficacy of anti-cancer drugs. However, the surrogacy of PFS/TTP for overall survival (OS) remains a matter of uncertainty in metastatic breast cancer (mBC). This study assessed the relationship between PFS/TTP and OS in mBC using a trial-based approach.
  
  
  METHODS
  WE CONDUCTED A SYSTEMATIC LITERATURE REVIEW ACCORDING TO THE PICO METHOD: 'Population' consisted of women with mBC; 'Interventions' and 'Comparators' were standard treatments for mBC or best supportive care; 'Outcomes' of interest were median PFS/TTP and OS. We first performed a correlation analysis between median PFS/TTP and OS, and then conducted subgroup analyses to explore possible reasons for heterogeneity. Then, we assessed the relationship between the treatment effect on PFS/TTP and OS. The treatment effect on PFS/TTP and OS was quantified by the absolute difference of median values. We also conducted linear regression analysis to predict the effects of a new anti-cancer drug on OS on the basis of its effects on PFS/TTP.
  
  
  RESULTS
  A total of 5,041 studies were identified, and 144 fulfilled the eligibility criteria. There was a statistically significant relationship between median PFS/TTP and OS across included trials (r=0.428; P<0.01). Correlation coefficient for the treatment effect on PFS/TTP and OS was estimated at 0.427 (P<0.01). The obtained linear regression equation was ΔOS =-0.088 (95% confidence interval [CI] -1.347-1.172) + 1.753 (95% CI 1.307-2.198) × ΔPFS (R(2)=0.86).
  
  
  CONCLUSIONS
  Results of this study indicate a significant association between PFS/TTP and OS in mBC, which may justify the use of PFS/TTP in the approval for commercialization and reimbursement of new anti-cancer drugs in this cancer setting.
authors: Université de Montréal, Faculté de pharmacie, Montreal, Montreal, QC, Canada.
authors: Catherine
authors: C
authors: Beauchemin
authors: Institut national d'excellence en santé et en services sociaux (INESSS), Montreal, QC, Canada.
authors: Dan
authors: D
authors: Cooper
authors: Université de Montréal, Faculté de pharmacie, Montreal, Montreal, QC, Canada.
authors: Marie-Ève
authors: MÈ
authors: Lapierre
authors: Centre Hospitalier de l'Université de Montréal - Hôpital Notre-Dame, Département de médecine, Université de Montréal, Montreal, QC, Canada.
authors: Louise
authors: L
authors: Yelle
authors: Université de Montréal, Faculté de pharmacie, Montreal, Montreal, QC, Canada.
authors: Jean
authors: J
authors: Lachaine
keywords: metastatic breast cancer; progression-free survival; surrogate endpoint; time to progression