Clinical trial end points for high-grade glioma: The evolving landscape

David A. Reardon, Evanthia Galanis, John F. DeGroot, Timothy F. Cloughesy, Jeffrey S. Wefel, Kathleen R. Lamborn, Andrew B. Lassman, Mark R. Gilbert, John H. Sampson, Wolfgang Wick, Marc C. Chamberlain, David R. Macdonald, Minesh P. Mehta, Michael A. Vogelbaum, Susan M. Chang, Martin J. Van Den Bent, Patrick Y. Wen

Research output: Contribution to journalArticle

79 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)353-361
Number of pages9
JournalNeuro-Oncology
Volume13
Issue number3
DOIs
StatePublished - Mar 2011

Fingerprint

Glioma
Clinical Trials
Survival
Salvage Therapy
Gold
Disease-Free Survival
Uncertainty
Patient Care
Therapeutics
Growth

Keywords

  • Clinical trials
  • End point
  • Malignant glioma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

Cite this

Reardon, D. A., Galanis, E., DeGroot, J. F., Cloughesy, T. F., Wefel, J. S., Lamborn, K. R., ... Wen, P. Y. (2011). Clinical trial end points for high-grade glioma: The evolving landscape. Neuro-Oncology, 13(3), 353-361. https://doi.org/10.1093/neuonc/noq203

Clinical trial end points for high-grade glioma : The evolving landscape. / Reardon, David A.; Galanis, Evanthia; DeGroot, John F.; Cloughesy, Timothy F.; Wefel, Jeffrey S.; Lamborn, Kathleen R.; Lassman, Andrew B.; Gilbert, Mark R.; Sampson, John H.; Wick, Wolfgang; Chamberlain, Marc C.; Macdonald, David R.; Mehta, Minesh P.; Vogelbaum, Michael A.; Chang, Susan M.; Van Den Bent, Martin J.; Wen, Patrick Y.

In: Neuro-Oncology, Vol. 13, No. 3, 03.2011, p. 353-361.

Research output: Contribution to journalArticle

Reardon, DA, Galanis, E, DeGroot, JF, Cloughesy, TF, Wefel, JS, Lamborn, KR, Lassman, AB, Gilbert, MR, Sampson, JH, Wick, W, Chamberlain, MC, Macdonald, DR, Mehta, MP, Vogelbaum, MA, Chang, SM, Van Den Bent, MJ & Wen, PY 2011, 'Clinical trial end points for high-grade glioma: The evolving landscape', Neuro-Oncology, vol. 13, no. 3, pp. 353-361. https://doi.org/10.1093/neuonc/noq203
Reardon DA, Galanis E, DeGroot JF, Cloughesy TF, Wefel JS, Lamborn KR et al. Clinical trial end points for high-grade glioma: The evolving landscape. Neuro-Oncology. 2011 Mar;13(3):353-361. https://doi.org/10.1093/neuonc/noq203
Reardon, David A. ; Galanis, Evanthia ; DeGroot, John F. ; Cloughesy, Timothy F. ; Wefel, Jeffrey S. ; Lamborn, Kathleen R. ; Lassman, Andrew B. ; Gilbert, Mark R. ; Sampson, John H. ; Wick, Wolfgang ; Chamberlain, Marc C. ; Macdonald, David R. ; Mehta, Minesh P. ; Vogelbaum, Michael A. ; Chang, Susan M. ; Van Den Bent, Martin J. ; Wen, Patrick Y. / Clinical trial end points for high-grade glioma : The evolving landscape. In: Neuro-Oncology. 2011 ; Vol. 13, No. 3. pp. 353-361.
@article{9d683fe2af36499a90bd8116ee9d5b5d,
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.",
keywords = "Clinical trials, End point, Malignant glioma",
author = "Reardon, {David A.} and Evanthia Galanis and DeGroot, {John F.} and Cloughesy, {Timothy F.} and Wefel, {Jeffrey S.} and Lamborn, {Kathleen R.} and Lassman, {Andrew B.} and Gilbert, {Mark R.} and Sampson, {John H.} and Wolfgang Wick and Chamberlain, {Marc C.} and Macdonald, {David R.} and Mehta, {Minesh P.} and Vogelbaum, {Michael A.} and Chang, {Susan M.} and {Van Den Bent}, {Martin J.} and Wen, {Patrick Y.}",
year = "2011",
month = "3",
doi = "10.1093/neuonc/noq203",
language = "English (US)",
volume = "13",
pages = "353--361",
journal = "Neuro-Oncology",
issn = "1522-8517",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - Clinical trial end points for high-grade glioma

T2 - The evolving landscape

AU - Reardon, David A.

AU - Galanis, Evanthia

AU - DeGroot, John F.

AU - Cloughesy, Timothy F.

AU - Wefel, Jeffrey S.

AU - Lamborn, Kathleen R.

AU - Lassman, Andrew B.

AU - Gilbert, Mark R.

AU - Sampson, John H.

AU - Wick, Wolfgang

AU - Chamberlain, Marc C.

AU - Macdonald, David R.

AU - Mehta, Minesh P.

AU - Vogelbaum, Michael A.

AU - Chang, Susan M.

AU - Van Den Bent, Martin J.

AU - Wen, Patrick Y.

PY - 2011/3

Y1 - 2011/3

N2 - 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.

AB - 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.

KW - Clinical trials

KW - End point

KW - Malignant glioma

UR - http://www.scopus.com/inward/record.url?scp=79955774313&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955774313&partnerID=8YFLogxK

U2 - 10.1093/neuonc/noq203

DO - 10.1093/neuonc/noq203

M3 - Article

C2 - 21310734

AN - SCOPUS:79955774313

VL - 13

SP - 353

EP - 361

JO - Neuro-Oncology

JF - Neuro-Oncology

SN - 1522-8517

IS - 3

ER -