Ovarian cancer clinical trial endpoints

Society of Gynecologic Oncology white paper

Thomas J. Herzog, Deborah K. Armstrong, Mark F. Brady, Robert L. Coleman, Mark H. Einstein, Bradley J. Monk, Robert S. Mannel, J. Tate Thigpen, Sharee A. Umpierre, Jeannine A. Villella, Ronald D. Alvarez

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Objective To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. Methods A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Results Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Conclusions Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect from active post-progression therapies. A large magnitude of effect in PFS improvement should establish benefit, and further communication with regulatory authorities to clarify acceptable endpoints should be undertaken.

Original languageEnglish (US)
Pages (from-to)8-17
Number of pages10
JournalGynecologic Oncology
Volume132
Issue number1
DOIs
StatePublished - Jan 2014

Fingerprint

Ovarian Neoplasms
Clinical Trials
Survival
Disease-Free Survival
Therapeutics
Communication
Quality of Life
Pharmaceutical Preparations

Keywords

  • Clinical trial endpoints
  • Ovarian cancer
  • Overall survival
  • Progression free survival

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Herzog, T. J., Armstrong, D. K., Brady, M. F., Coleman, R. L., Einstein, M. H., Monk, B. J., ... Alvarez, R. D. (2014). Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper. Gynecologic Oncology, 132(1), 8-17. https://doi.org/10.1016/j.ygyno.2013.11.008

Ovarian cancer clinical trial endpoints : Society of Gynecologic Oncology white paper. / Herzog, Thomas J.; Armstrong, Deborah K.; Brady, Mark F.; Coleman, Robert L.; Einstein, Mark H.; Monk, Bradley J.; Mannel, Robert S.; Thigpen, J. Tate; Umpierre, Sharee A.; Villella, Jeannine A.; Alvarez, Ronald D.

In: Gynecologic Oncology, Vol. 132, No. 1, 01.2014, p. 8-17.

Research output: Contribution to journalArticle

Herzog, TJ, Armstrong, DK, Brady, MF, Coleman, RL, Einstein, MH, Monk, BJ, Mannel, RS, Thigpen, JT, Umpierre, SA, Villella, JA & Alvarez, RD 2014, 'Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper', Gynecologic Oncology, vol. 132, no. 1, pp. 8-17. https://doi.org/10.1016/j.ygyno.2013.11.008
Herzog TJ, Armstrong DK, Brady MF, Coleman RL, Einstein MH, Monk BJ et al. Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper. Gynecologic Oncology. 2014 Jan;132(1):8-17. https://doi.org/10.1016/j.ygyno.2013.11.008
Herzog, Thomas J. ; Armstrong, Deborah K. ; Brady, Mark F. ; Coleman, Robert L. ; Einstein, Mark H. ; Monk, Bradley J. ; Mannel, Robert S. ; Thigpen, J. Tate ; Umpierre, Sharee A. ; Villella, Jeannine A. ; Alvarez, Ronald D. / Ovarian cancer clinical trial endpoints : Society of Gynecologic Oncology white paper. In: Gynecologic Oncology. 2014 ; Vol. 132, No. 1. pp. 8-17.
@article{cb10d9fbb4614b7f8854ef93dcf849a4,
title = "Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper",
abstract = "Objective To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. Methods A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Results Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Conclusions Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect from active post-progression therapies. A large magnitude of effect in PFS improvement should establish benefit, and further communication with regulatory authorities to clarify acceptable endpoints should be undertaken.",
keywords = "Clinical trial endpoints, Ovarian cancer, Overall survival, Progression free survival",
author = "Herzog, {Thomas J.} and Armstrong, {Deborah K.} and Brady, {Mark F.} and Coleman, {Robert L.} and Einstein, {Mark H.} and Monk, {Bradley J.} and Mannel, {Robert S.} and Thigpen, {J. Tate} and Umpierre, {Sharee A.} and Villella, {Jeannine A.} and Alvarez, {Ronald D.}",
year = "2014",
month = "1",
doi = "10.1016/j.ygyno.2013.11.008",
language = "English (US)",
volume = "132",
pages = "8--17",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Ovarian cancer clinical trial endpoints

T2 - Society of Gynecologic Oncology white paper

AU - Herzog, Thomas J.

AU - Armstrong, Deborah K.

AU - Brady, Mark F.

AU - Coleman, Robert L.

AU - Einstein, Mark H.

AU - Monk, Bradley J.

AU - Mannel, Robert S.

AU - Thigpen, J. Tate

AU - Umpierre, Sharee A.

AU - Villella, Jeannine A.

AU - Alvarez, Ronald D.

PY - 2014/1

Y1 - 2014/1

N2 - Objective To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. Methods A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Results Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Conclusions Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect from active post-progression therapies. A large magnitude of effect in PFS improvement should establish benefit, and further communication with regulatory authorities to clarify acceptable endpoints should be undertaken.

AB - Objective To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. Methods A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Results Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Conclusions Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect from active post-progression therapies. A large magnitude of effect in PFS improvement should establish benefit, and further communication with regulatory authorities to clarify acceptable endpoints should be undertaken.

KW - Clinical trial endpoints

KW - Ovarian cancer

KW - Overall survival

KW - Progression free survival

UR - http://www.scopus.com/inward/record.url?scp=84892795291&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84892795291&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2013.11.008

DO - 10.1016/j.ygyno.2013.11.008

M3 - Article

VL - 132

SP - 8

EP - 17

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 1

ER -