Background: Clinical trials in advanced/metastatic urothelial cancer have been difficult to perform. We review the current characteristics of randomized controlled trials (RCTs) and evaluate whether PFS could be a potential surrogate endpoint for overall survival (OS) in advanced/metastatic urothelial cancer. Methods: We identified trials by a systematic review of Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to April 2017. We included RCTs of patients with locally advanced/metastatic urothelial cancer that involved systemic therapy as an intervention, and those with reported hazards ratios (HRs) and corresponding 95% confidence intervals (CIs) for both OS and PFS, or provided Kaplan-Meier curves from which HRs and 95% CI could be calculated. The correlation coefficient between log of HRs for OS and PFS was calculated using linear regression weighted by sample size. Results: Forty eight trials that enrolled 7019 patients were included in the review and 24 RCTs were included in the surrogacy analysis. 27(56.3%) of identified 48 RCTs were phase II trials, and the median sample size was 107(range, 30-626) for all RCTs. The correlation coefficient between log HR for PFS and log HR for OS was 0.79 (95% CI, 0.58-0.91). The correlation coefficient increased to 0.87 (95% CI, 0.72-0.94) after excluding the only trial with immune checkpoint inhibitor. Multiple sensitivity analyses did not change the results..aph."/ > Conclusions: PFS is strongly correlated with OS in trials of advanced/metastatic urothelial cancer assessing the treatment benefit of new drugs And PFS warrants further exploration as a surrogate endpoint in clinical trial datasets.
[1]Fudan Univ, Shanghai Canc Ctr, Shanghai, Peoples R China;
[2]Fudan Univ, Shanghai Med Coll, Shanghai, Peoples R China;
[3]Qingdao Univ, Affiliated Hosp, Qingdao, Peoples R China
(8.0+极速模式)