Progression-Free Survival and Time to Progression as Real Surrogate End Points for Overall Survival in Advanced Breast Cancer: A Meta-Analysis of 37 Trials

Background Progression-free survival (PFS) and time to progression (TTP) have been reported to correlate with overall survival (OS) in several cancer types. To our knowledge, however, the correlation between them is unclear. Methods A literature-based meta-analysis was performed to assess whether PFS and TTP can be considered reliable surrogate end points for OS in a phase 3 clinical trial of advanced breast cancer (ABC). The median hazard ratios of PFS/TTP and OS were analyzed by determining their nonparametric Spearman rank correlation coefficients (Rs). Results A total of 37 trials with 38 treatment arms and 14,966 patients were selected for analysis. The Rs between the median PFS/TTP and OS was 0.405 (95% confidence interval [CI], 0.191-0.582; P = .003), and the correlation coefficient between the hazard ratios of PFS/TTP and OS was 0.555 (95% CI, 0.277-0.748; P = .003). PFS/TTP was closely correlated with OS in the trials of targeted therapy-based treatment (Rs = 0.872; 95% CI, 0.619-0.962; P = .0001) and of PFS/TTP or OS benefit (Rs = 0.753 and Rs = 0.821, respectively) for ABC. Conclusions Both PFS and TTP can be considered valid surrogate end points for OS in the trials of targeted therapy-based treatments and clinical benefits for ABC. Further research is necessary to clarify the surrogacy of PFS/TTP for OS in other trials of targeted therapy-based treatments for ABC.