title: Progression-free survival as surrogate and as true end point: insights from the breast and colorectal cancer literature.
abstract: Significant achievements in the systemic treatment of both advanced breast cancer and advanced colorectal cancer over the past 10 years have led to a growing number of drugs, combinations, and sequences to be tested. The choice of surrogate and true end points has become a critical issue and one that is currently the subject of much debate. Many recent randomized trials in solid tumor oncology have used progression-free survival (PFS) as the primary end point. PFS is an attractive end point because it is available earlier than overall survival (OS) and is not influenced by second-line treatments. PFS is now undergoing validation as a surrogate end point in various disease settings. The question of whether PFS can be considered an acceptable surrogate end point depends not only on formal validation studies but also on a standardized definition and unbiased ascertainment of disease progression in clinical trials. In advanced breast cancer, formal validation of PFS as a surrogate for OS has so far been unsuccessful. In advanced colorectal cancer, in contrast, current evidence indicates that PFS is a valid surrogate for OS after first-line treatment with chemotherapy. The other question is whether PFS sufficiently reflects clinical benefit to be considered a true end point in and of itself.
authors.affiliation: Dendrix Research, Hospital Sírio-Libanes, Sao Paulo, Brazil. everardo@dendrix.com.br
authors.forename: E D
authors.initials: ED
authors.lastname: Saad
authors.forename: A
authors.initials: A
authors.lastname: Katz
authors.forename: P M
authors.initials: PM
authors.lastname: Hoff
authors.forename: M
authors.initials: M
authors.lastname: Buyse
mesh_terms: D015415:Biomarkers; D001943:Breast Neoplasms / Q000401:mortality*; D015179:Colorectal Neoplasms / Q000401:mortality*; D018572:Disease-Free Survival; D015340:Epidemiologic Research Design; D005260:Female; D006801:Humans; D016032:Randomized Controlled Trials as Topic
chemical_list: D015415:Biomarkers