Is there consensus in the definition of endpoints in metastatic breast cancer?.

Abstract

Abstract Abstract #3102 Objective: Progression-free survival (PFS) is defined as the time between treatment initiation and tumor progression or death from any cause, with censoring of patients who are lost to follow-up. Time to tumor progression (TTP) is theoretically different from PFS in that the event of interest is only disease progression. Both PFS and TTP have been considered as appropriate endpoints in drug development, but the extent to which investigators agree on their definition is unknown. We therefore assessed the recent literature regarding the consistence of the definition of PFS and TTP when used as primary endpoints in advanced breast cancer.
 Methods: We searched PubMed using the medical subject headings “breast neoplasms” and “drug therapy”, limiting the search to phase III trials on systemic antineoplastic therapies published between January 1, 2000, and December 31, 2007 in one of ten leading medical journals in the field (Annals of Oncology, Breast Cancer Research and Treatment, British Journal of Cancer, Cancer, European Journal of Cancer, Journal of Clinical Oncology, Journal of the National Cancer Institute, Lancet Oncology, The Lancet and The New England Journal of Medicine). We excluded randomized phase II trials, factorial trials, studies on high-dose chemotherapy, papers reporting combined analyses of two or more separate trials, and companion studies on correlative biology or prognostic factors.
 Results: The search yielded 59 trials enrolling a total of 23,371 evaluable patients in 122 treatment arms. PFS was the primary endpoint in 14 cases, and TTP in 21 when all treatment lines and modalities were considered (response rate was used in 20 cases, and overall survival in only one). For first-line chemotherapy trials (N=24), PFS and TTP were used as primary endpoints in 5 and 7 cases, respectively. In 5 of the 21 trials using TTP as the primary endpoint, no definition of this endpoint was reported in the article. Analysis of the other 16 cases showed that progressive disease was always considered an event in TTP analysis. However, in 13 of these cases, death (either from breast cancer or from any cause) was also counted as an event. The definition of PFS was reported in the article in 13 of the 14 trials using this primary endpoint. In all cases, the events of interest in Kaplan-Meier analyses included both progressive disease and death. In some cases, both terms (PFS and TTP) were even used to denote the same endpoint in the same paper.
 Conclusion: Our review suggests that investigators are frequently using PFS and TTP interchangeably in metastatic breast cancer. Such use of terms may lead to confusion when results of different trials are evaluated in perspective, and standardization of the definitions seems therefore in order. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3102.