title: When progressive disease does not mean treatment failure: reconsidering the criteria for progression.
abstract: Although progression-based endpoints, such as progression-free survival, are often key clinical trial endpoints for anticancer agents, the clinical meaning of "objective progression" is much less certain. As scrutiny of progression-based endpoints in clinical trials increases, it should be remembered that the Response Evaluation Criteria In Solid Tumors (RECIST) progression criteria were not developed as a surrogate for survival. Now that progression-free survival has come to be an increasingly important trial endpoint, the criteria that define progression deserve critical evaluation to determine whether alternate definitions of progression might facilitate the development of stronger surrogate endpoints and more meaningful trial results. In this commentary, we review the genesis of the criteria for progression, highlight recent data that question their value as a marker of treatment failure, and advocate for several research strategies that could lay the groundwork for a clinically validated definition of disease progression in solid tumor oncology.
authors.affiliation: Dana-Farber Cancer Institute, 450 Brookline Ave., Dana 1234, Boston, MA 02215, USA. Geoffrey_Oxnard@DFCI.Harvard.edu
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Oxnard
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morris
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Baker
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Alan P
authors.initials: AP
authors.lastname: Venook
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Schwartz
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D006801:Humans; D000074324:Ipilimumab; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D000077594:Nivolumab; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D012107:Research Design / Q000592:standards; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab; D000077594:Nivolumab; D066246:ErbB Receptors; D017430:Prostate-Specific Antigen