title: Clinical trial end points for high-grade glioma: the evolving landscape.
abstract: To review the strengths and weaknesses of primary and auxiliary end points for clinical trials among patients with high-grade glioma (HGG). Recent advances in outcome for patients with newly diagnosed and recurrent HGG, coupled with the development of multiple promising therapeutics with myriad antitumor actions, have led to significant growth in the number of clinical trials for patients with HGG. Appropriate clinical trial design and the incorporation of optimal end points are imperative to efficiently and effectively evaluate such agents and continue to advance outcome. Growing recognition of limitations weakening the reliability of traditional clinical trial primary end points has generated increasing uncertainty of how best to evaluate promising therapeutics for patients with HGG. The phenomena of pseudoprogression and pseudoresponse have made imaging-based end points, including overall radiographic response and progression-free survival, problematic. Although overall survival is considered the "gold-standard" end point, recently identified active salvage therapies such as bevacizumab may diminish the association between presalvage therapy and overall survival. Finally, advances in imaging as well as the assessment of patient function and well being have strengthened interest in auxiliary end points assessing these aspects of patient care and outcome. Better appreciation of the strengths and limitations of primary end points will lead to more effective clinical trial strategies. Technical advances in imaging as well as improved survival for patients with HGG support the further development of auxiliary end points evaluating novel imaging approaches as well as measures of patient function and well being.
authors.affiliation: The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Box 3624, Durham, NC 27710, USA. reard003@mc.duke.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.forename: Evanthia
authors.initials: E
authors.lastname: Galanis
authors.forename: John F
authors.initials: JF
authors.lastname: DeGroot
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Cloughesy
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Wefel
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Lamborn
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Lassman
authors.forename: Mark R
authors.initials: MR
authors.lastname: Gilbert
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.forename: Marc C
authors.initials: MC
authors.lastname: Chamberlain
authors.forename: David R
authors.initials: DR
authors.lastname: Macdonald
authors.forename: Minesh P
authors.initials: MP
authors.lastname: Mehta
authors.forename: Michael A
authors.initials: MA
authors.lastname: Vogelbaum
authors.forename: Susan M
authors.initials: SM
authors.lastname: Chang
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Van den Bent
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
mesh_terms: D001932:Brain Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D002986:Clinical Trials as Topic; D005910:Glioma / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D006801:Humans; D016879:Salvage Therapy; D015996:Survival Rate