Progression-free survival and time to progression as primary end points in advanced breast cancer: often used, sometimes loosely defined

Backgound: The growing availability of active agents makes the development of novel therapies increasingly complex and the choice of end points critical. We assessed the frequency of use of efficacy end points in advanced breast cancer. Methods: We searched PubMed for randomized trials published between 2000 and 2007 in 10 leading medical journals. We abstracted data on progression-free survival (PFS), time to tumor progression (TTP), response rate (RR) and overall survival. Results: A total of 58 studies enrolled 23 371 assessable patients in 122 treatment arms. The primary end points most frequently used were RR and TTP (n = 21 each), followed by PFS (n = 14). In five of the trials using TTP as the primary end point, no definition of TTP was reported; in 13 of the other 16 cases, death was counted as an event, making TTP indistinguishable from PFS. Trials having PFS, TTP or time to treatment failure as the primary end point (n = 36) had a higher mean number of patients than those using RR (P = 0.061). Conclusion: Investigators seem to be frequently using PFS and TTP interchangeably in advanced breast cancer. Such use of terms may lead to confusion when results of different trials are compared, and uniform use of definitions seems in order.