Disease-free survival as a surrogate endpoint for overall survival in adjuvant trials of pancreatic cancer: a meta-analysis of 20 randomized controlled trials

• Published in: BMC cancer Vol. 20; no. 1; p. 421
• Main Authors: Nie, Run-Cong, Zou, Xue-Bin, Yuan, Shu-Qiang, Chen, Ying-Bo, Chen, Shi, Chen, Yong-Ming, Chen, Guo-Ming, Chen, Xiao-Jiang, Luo, Tian-Qi, Li, Shu-Man, Duan, Jin-Ling, Wang, Yun, Li, Yuan-Fang
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.05.2020; BioMed Central; BMC
• Subjects: Analysis; Biomarkers - analysis; Biomarkers, Tumor - genetics; Cancer metastasis; Cancer therapies; Chemotherapy; Chemotherapy, Adjuvant - mortality; Clinical trials; Confidence intervals; Disease-free survival; Humans; Medical research; Meta-analysis; Metastases; Metastasis; Overall survival; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - mortality; Patient outcomes; Prognosis; Randomized Controlled Trials as Topic; Sensitivity analysis; Studies; Surrogate; Survival; Survival Rate; Overall survival; Surrogate; Pancreatic cancer; Disease-free survival
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-020-06910-5

We aimed to assess whether disease-free survival (DFS) could serve as a reliable surrogate endpoint for overall survival (OS) in adjuvant trials of pancreatic cancer. We systematically reviewed adjuvant randomized trials for non-metastatic pancreatic cancer after curative resection that reported a hazard ratio (HR) for DFS and OS. We assessed the correlation between treatment effect (HR) on DFS and OS, weighted by sample size or precision of hazard ratio estimate, assuming fixed and random effects, and calculated the surrogate threshold effect (STE). We also performed sensitivity analyses and a leave-one-out cross validation approach to evaluate the robustness of our findings. After screening 450 relevant articles, we identified a total of 20 qualifying trails comprising 5170 patients for quantitative analysis. We noted a strong correlation between the treatment effects for DFS and OS, with coefficient of determination of 0.82 in the random effect model, 0.82 in the fixed effect model, and 0.80 in the sample size weighting; the robustness of this finding was further verified by the leave-one-out cross-validation approach. Sensitivity analyses with restriction to phase 3 trials, large trials, trials with mature follow-up periods, and trials with adjuvant therapy versus adjuvant therapy strengthened the correlation (0.75 to 0.88) between DFS and OS. The STE was 0.96 for DFS. Therefore, DFS could be regarded as a surrogate endpoint for OS in adjuvant trials of pancreatic cancer. In future similar adjuvant trials, a hazard ratio for DFS of 0.96 or less would predict a treatment impact on OS.