title: Progression-free survival as surrogate endpoint in advanced pancreatic cancer: meta-analysis of 30 randomized first-line trials.
abstract: BACKGROUND
  Progression-free survival (PFS) has not been extensively investigated as a surrogate for survival in the first-line treatments of pancreatic cancer. The aim of this review was to evaluate PFS as a potential surrogate endpoint for overall survival (OS) in advanced pancreatic cancer in trials comparing poly-chemotherapy to gemcitabine alone.
  
  
  METHODS
  A systematic literature search in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials was conducted. The key words included randomized trial, first-line chemotherapy, pancreatic cancer, gemcitabine and poly-chemotherapy. Adjusted weighted linear regression was used to calculate RS (Spearman's rank-order correlation coefficient) between PFS and post-progression survival (PPS) with OS (RS) and between treatment effects on PFS and OS (RHR).
  
  
  RESULTS
  A total of 30 trials including 8467 patients met the inclusion criteria. Correlation between the treatment effects on PFS and OS (RHR=0.78) and between the endpoint PFS and OS was high across all studies (RS=0.75). The slope of the regression line was 0.76+/-0.26, indicating that an agent producing a 10% risk reduction for PFS will provide a 7.6%+/-2.6% risk reduction for OS. Correlation between PPS and OS was very strong (RS=0.71) and accounted for more than 50% of the whole OS variability (R2=0.57).
  
  
  CONCLUSIONS
  Because of the robust correlation with OS and the potential influence of PPS caused by the second line therapies, it may be justified to consider PFS as a surrogate endpoint in trials evaluating new cytotoxic agents when gemcitabine is the control arm.
authors: Medical Oncology Unit, Oncology Department, Azienda Ospedaliera Treviglio, Piazzale Ospedale 1, 24047 Treviglio (BG), Italy. faupe@libero.it.
authors: Fausto
authors: F
authors: Petrelli
authors: Andrea
authors: A
authors: Coinu
authors: Karen
authors: K
authors: Borgonovo
authors: Mary
authors: M
authors: Cabiddu
authors: Sandro
authors: S
authors: Barni
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D013534:Survival; D000093542:Gemcitabine
chemical_list: D015415:Biomarkers; D003841:Deoxycytidine; D000093542:Gemcitabine