Influence of censoring on conclusions of trials for women with metastatic breast cancer.

Progression-free survival and time-to-progression (PFS/TTP) are used commonly as primary end-points in trials evaluating treatments for metastatic breast cancer (MBC). We reviewed the impact of censoring on interpretation of these end-points. A systematic review identified phase 3 trials in MBC published between 2001 and 2012 that reported hazard ratios (HRs) for PFS/TTP and Kaplan-Meier curves indicating numbers at risk. We calculated HRs for time-to-treatment-failure (TTF) where discontinuation of treatment for any reason is considered an event. Mean HRs for PFS/TTP, TTF, and overall survival (OS) were 0.79, 0.89 and 0.91, respectively. Unbalanced censoring of patients prior to progression was prevalent, usually with more patients censored in the experimental arms. There was moderate-to-poor correlation of HRs of PFS/TTP and TTF with HRs for OS. We suggest that TTF should be reported as supportive analysis in registration trials and extent of missing data due to censoring be considered in decisions made by regulatory agencies.