Individual patient data analysis of progression-free survival versus overall survival as a first-line end point for metastatic colorectal cancer in modern randomized trials: Findings from the analysis and research in cancers of the digestive system database

Qian D Shi, Aimery De Gramont, Axel F Grothey, John Zalcberg, Benoist Chibaudel, Hans Joachim Schmoll, Matthew T. Seymour, Richard Adams, Leonard Saltz, Richard M. Goldberg, Cornelis J A Punt, Jean Yves Douillard, Paulo M. Hoff, Joel Randolph Hecht, Herbert Hurwitz, Eduardo Díaz-Rubio, Rainer Porschen, Niall C. Tebbutt, Charles Fuchs, John SouglakosAlfredo Falcone, Christophe Tournigand, Fairooz F. Kabbinavar, Volker Heinemann, Eric Van Cutsem, Carsten Bokemeyer, Marc Buyse, Daniel J. Sargent

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Purpose: Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Methods: Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti-epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R2 statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Results: Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R2, 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. Conclusion: In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents.

Original languageEnglish (US)
Pages (from-to)22-28
Number of pages7
JournalJournal of Clinical Oncology
Volume33
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

Digestive System Neoplasms
Disease-Free Survival
Colorectal Neoplasms
Databases
Survival
Research
Biological Factors
Therapeutics
Least-Squares Analysis
Proportional Hazards Models
Epidermal Growth Factor Receptor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Individual patient data analysis of progression-free survival versus overall survival as a first-line end point for metastatic colorectal cancer in modern randomized trials : Findings from the analysis and research in cancers of the digestive system database. / Shi, Qian D; De Gramont, Aimery; Grothey, Axel F; Zalcberg, John; Chibaudel, Benoist; Schmoll, Hans Joachim; Seymour, Matthew T.; Adams, Richard; Saltz, Leonard; Goldberg, Richard M.; Punt, Cornelis J A; Douillard, Jean Yves; Hoff, Paulo M.; Hecht, Joel Randolph; Hurwitz, Herbert; Díaz-Rubio, Eduardo; Porschen, Rainer; Tebbutt, Niall C.; Fuchs, Charles; Souglakos, John; Falcone, Alfredo; Tournigand, Christophe; Kabbinavar, Fairooz F.; Heinemann, Volker; Van Cutsem, Eric; Bokemeyer, Carsten; Buyse, Marc; Sargent, Daniel J.

In: Journal of Clinical Oncology, Vol. 33, No. 1, 01.01.2015, p. 22-28.

Research output: Contribution to journalArticle

Shi, QD, De Gramont, A, Grothey, AF, Zalcberg, J, Chibaudel, B, Schmoll, HJ, Seymour, MT, Adams, R, Saltz, L, Goldberg, RM, Punt, CJA, Douillard, JY, Hoff, PM, Hecht, JR, Hurwitz, H, Díaz-Rubio, E, Porschen, R, Tebbutt, NC, Fuchs, C, Souglakos, J, Falcone, A, Tournigand, C, Kabbinavar, FF, Heinemann, V, Van Cutsem, E, Bokemeyer, C, Buyse, M & Sargent, DJ 2015, 'Individual patient data analysis of progression-free survival versus overall survival as a first-line end point for metastatic colorectal cancer in modern randomized trials: Findings from the analysis and research in cancers of the digestive system database', Journal of Clinical Oncology, vol. 33, no. 1, pp. 22-28. https://doi.org/10.1200/JCO.2014.56.5887
Shi, Qian D ; De Gramont, Aimery ; Grothey, Axel F ; Zalcberg, John ; Chibaudel, Benoist ; Schmoll, Hans Joachim ; Seymour, Matthew T. ; Adams, Richard ; Saltz, Leonard ; Goldberg, Richard M. ; Punt, Cornelis J A ; Douillard, Jean Yves ; Hoff, Paulo M. ; Hecht, Joel Randolph ; Hurwitz, Herbert ; Díaz-Rubio, Eduardo ; Porschen, Rainer ; Tebbutt, Niall C. ; Fuchs, Charles ; Souglakos, John ; Falcone, Alfredo ; Tournigand, Christophe ; Kabbinavar, Fairooz F. ; Heinemann, Volker ; Van Cutsem, Eric ; Bokemeyer, Carsten ; Buyse, Marc ; Sargent, Daniel J. / Individual patient data analysis of progression-free survival versus overall survival as a first-line end point for metastatic colorectal cancer in modern randomized trials : Findings from the analysis and research in cancers of the digestive system database. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 1. pp. 22-28.
@article{2e0f71aa5cca47ab8193cef8227ccf6a,
title = "Individual patient data analysis of progression-free survival versus overall survival as a first-line end point for metastatic colorectal cancer in modern randomized trials: Findings from the analysis and research in cancers of the digestive system database",
abstract = "Purpose: Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Methods: Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti-epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R2 statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Results: Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R2, 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. Conclusion: In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents.",
author = "Shi, {Qian D} and {De Gramont}, Aimery and Grothey, {Axel F} and John Zalcberg and Benoist Chibaudel and Schmoll, {Hans Joachim} and Seymour, {Matthew T.} and Richard Adams and Leonard Saltz and Goldberg, {Richard M.} and Punt, {Cornelis J A} and Douillard, {Jean Yves} and Hoff, {Paulo M.} and Hecht, {Joel Randolph} and Herbert Hurwitz and Eduardo D{\'i}az-Rubio and Rainer Porschen and Tebbutt, {Niall C.} and Charles Fuchs and John Souglakos and Alfredo Falcone and Christophe Tournigand and Kabbinavar, {Fairooz F.} and Volker Heinemann and {Van Cutsem}, Eric and Carsten Bokemeyer and Marc Buyse and Sargent, {Daniel J.}",
year = "2015",
month = "1",
day = "1",
doi = "10.1200/JCO.2014.56.5887",
language = "English (US)",
volume = "33",
pages = "22--28",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "1",

}

TY - JOUR

T1 - Individual patient data analysis of progression-free survival versus overall survival as a first-line end point for metastatic colorectal cancer in modern randomized trials

T2 - Findings from the analysis and research in cancers of the digestive system database

AU - Shi, Qian D

AU - De Gramont, Aimery

AU - Grothey, Axel F

AU - Zalcberg, John

AU - Chibaudel, Benoist

AU - Schmoll, Hans Joachim

AU - Seymour, Matthew T.

AU - Adams, Richard

AU - Saltz, Leonard

AU - Goldberg, Richard M.

AU - Punt, Cornelis J A

AU - Douillard, Jean Yves

AU - Hoff, Paulo M.

AU - Hecht, Joel Randolph

AU - Hurwitz, Herbert

AU - Díaz-Rubio, Eduardo

AU - Porschen, Rainer

AU - Tebbutt, Niall C.

AU - Fuchs, Charles

AU - Souglakos, John

AU - Falcone, Alfredo

AU - Tournigand, Christophe

AU - Kabbinavar, Fairooz F.

AU - Heinemann, Volker

AU - Van Cutsem, Eric

AU - Bokemeyer, Carsten

AU - Buyse, Marc

AU - Sargent, Daniel J.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Purpose: Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Methods: Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti-epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R2 statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Results: Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R2, 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. Conclusion: In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents.

AB - Purpose: Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Methods: Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti-epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R2 statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Results: Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R2, 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. Conclusion: In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents.

UR - http://www.scopus.com/inward/record.url?scp=84920602447&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84920602447&partnerID=8YFLogxK

U2 - 10.1200/JCO.2014.56.5887

DO - 10.1200/JCO.2014.56.5887

M3 - Article

C2 - 25385741

AN - SCOPUS:84920602447

VL - 33

SP - 22

EP - 28

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 1

ER -