BACKGROUND:Progression-free survival (PFS) has not been extensively investigated as a surrogate for survival in the ifrst-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. DATA SOURCES: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, ifrst-line chemotherapy, pancreatic cancer, gemcitabine and poly-chemotherapy. Adjusted weighted linear regression was used to calculate RS (Spearmans rank-order correlation coefifcient) 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 re-gression line was 0.76±0.26, indicating that an agent produc-ing 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). CONCLUSION:Because of the robust correlation with OS and the potential inlfuence of PPS caused by the second line therapies, it may be justiifed to consider PFS as a surrogate endpoint in trials evaluating new cytotoxic agents when gem-citabine is the control arm.