Progression-free survival as surrogate endpoint in advanced pancreatic cancer: meta-analysis of 30 randomized first-line trials

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. 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, first-line chemotherapy, pancreatic cancer, gemcitabine and poly-chemotherapy. Adjusted weighted linear regression was used to calculate R-s (Spearman's rank-order correlation coefficient) between PFS and post-progression survival (PPS) with OS (R-s) and between treatment effects on PFS and OS (R-HR). RESULTS: A total of 30 trials including 8467 patients met the inclusion criteria. Correlation between the treatment effects on PFS and OS (R-HR=0.78) and between the endpoint PFS and OS was high across all studies (R-s=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 (R-s=0.71) and accounted for more than 50% of the whole OS variability (R-2=0.57). CONCLUSION: 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.