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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

Identifieur interne : 003808 ( Main/Exploration ); précédent : 003807; suivant : 003809

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

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

Source :

RBID : PMC:4482837

Descripteurs français

English descriptors

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.


Url:
DOI: 10.1200/JCO.2014.56.5887
PubMed: 25385741
PubMed Central: 4482837


Affiliations:


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<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
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<name sortKey="Zalcberg, John" sort="Zalcberg, John" uniqKey="Zalcberg J" first="John" last="Zalcberg">John Zalcberg</name>
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<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
<wicri:regionArea>Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve</wicri:regionArea>
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<name sortKey="Chibaudel, Benoist" sort="Chibaudel, Benoist" uniqKey="Chibaudel B" first="Benoist" last="Chibaudel">Benoist Chibaudel</name>
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<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
<wicri:regionArea>Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve</wicri:regionArea>
<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Schmoll, Hans Joachim" sort="Schmoll, Hans Joachim" uniqKey="Schmoll H" first="Hans-Joachim" last="Schmoll">Hans-Joachim Schmoll</name>
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<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
<wicri:regionArea>Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve</wicri:regionArea>
<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Seymour, Matthew T" sort="Seymour, Matthew T" uniqKey="Seymour M" first="Matthew T." last="Seymour">Matthew T. Seymour</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
<wicri:regionArea>Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve</wicri:regionArea>
<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Adams, Richard" sort="Adams, Richard" uniqKey="Adams R" first="Richard" last="Adams">Richard Adams</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
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<author>
<name sortKey="Saltz, Leonard" sort="Saltz, Leonard" uniqKey="Saltz L" first="Leonard" last="Saltz">Leonard Saltz</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
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<author>
<name sortKey="Goldberg, Richard M" sort="Goldberg, Richard M" uniqKey="Goldberg R" first="Richard M." last="Goldberg">Richard M. Goldberg</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Punt, Cornelis J A" sort="Punt, Cornelis J A" uniqKey="Punt C" first="Cornelis J. A." last="Punt">Cornelis J. A. Punt</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Douillard, Jean Yves" sort="Douillard, Jean Yves" uniqKey="Douillard J" first="Jean-Yves" last="Douillard">Jean-Yves Douillard</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Hoff, Paulo M" sort="Hoff, Paulo M" uniqKey="Hoff P" first="Paulo M." last="Hoff">Paulo M. Hoff</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Hecht, Joel Randolph" sort="Hecht, Joel Randolph" uniqKey="Hecht J" first="Joel Randolph" last="Hecht">Joel Randolph Hecht</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Hurwitz, Herbert" sort="Hurwitz, Herbert" uniqKey="Hurwitz H" first="Herbert" last="Hurwitz">Herbert Hurwitz</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Diaz Rubio, Eduardo" sort="Diaz Rubio, Eduardo" uniqKey="Diaz Rubio E" first="Eduardo" last="Díaz-Rubio">Eduardo Díaz-Rubio</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
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<author>
<name sortKey="Porschen, Rainer" sort="Porschen, Rainer" uniqKey="Porschen R" first="Rainer" last="Porschen">Rainer Porschen</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
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<author>
<name sortKey="Tebbutt, Niall C" sort="Tebbutt, Niall C" uniqKey="Tebbutt N" first="Niall C." last="Tebbutt">Niall C. Tebbutt</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Fuchs, Charles" sort="Fuchs, Charles" uniqKey="Fuchs C" first="Charles" last="Fuchs">Charles Fuchs</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
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<author>
<name sortKey="Souglakos, John" sort="Souglakos, John" uniqKey="Souglakos J" first="John" last="Souglakos">John Souglakos</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Falcone, Alfredo" sort="Falcone, Alfredo" uniqKey="Falcone A" first="Alfredo" last="Falcone">Alfredo Falcone</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Tournigand, Christophe" sort="Tournigand, Christophe" uniqKey="Tournigand C" first="Christophe" last="Tournigand">Christophe Tournigand</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Kabbinavar, Fairooz F" sort="Kabbinavar, Fairooz F" uniqKey="Kabbinavar F" first="Fairooz F." last="Kabbinavar">Fairooz F. Kabbinavar</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Heinemann, Volker" sort="Heinemann, Volker" uniqKey="Heinemann V" first="Volker" last="Heinemann">Volker Heinemann</name>
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<title xml:lang="en" level="a" type="main">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</title>
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<name sortKey="Shi, Qian" sort="Shi, Qian" uniqKey="Shi Q" first="Qian" last="Shi">Qian Shi</name>
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<name sortKey="Grothey, Axel" sort="Grothey, Axel" uniqKey="Grothey A" first="Axel" last="Grothey">Axel Grothey</name>
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<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Zalcberg, John" sort="Zalcberg, John" uniqKey="Zalcberg J" first="John" last="Zalcberg">John Zalcberg</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Chibaudel, Benoist" sort="Chibaudel, Benoist" uniqKey="Chibaudel B" first="Benoist" last="Chibaudel">Benoist Chibaudel</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Schmoll, Hans Joachim" sort="Schmoll, Hans Joachim" uniqKey="Schmoll H" first="Hans-Joachim" last="Schmoll">Hans-Joachim Schmoll</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Seymour, Matthew T" sort="Seymour, Matthew T" uniqKey="Seymour M" first="Matthew T." last="Seymour">Matthew T. Seymour</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Adams, Richard" sort="Adams, Richard" uniqKey="Adams R" first="Richard" last="Adams">Richard Adams</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Saltz, Leonard" sort="Saltz, Leonard" uniqKey="Saltz L" first="Leonard" last="Saltz">Leonard Saltz</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
<wicri:regionArea>Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve</wicri:regionArea>
<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Goldberg, Richard M" sort="Goldberg, Richard M" uniqKey="Goldberg R" first="Richard M." last="Goldberg">Richard M. Goldberg</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
<wicri:regionArea>Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve</wicri:regionArea>
<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Punt, Cornelis J A" sort="Punt, Cornelis J A" uniqKey="Punt C" first="Cornelis J. A." last="Punt">Cornelis J. A. Punt</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
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<author>
<name sortKey="Douillard, Jean Yves" sort="Douillard, Jean Yves" uniqKey="Douillard J" first="Jean-Yves" last="Douillard">Jean-Yves Douillard</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
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<author>
<name sortKey="Hoff, Paulo M" sort="Hoff, Paulo M" uniqKey="Hoff P" first="Paulo M." last="Hoff">Paulo M. Hoff</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Hecht, Joel Randolph" sort="Hecht, Joel Randolph" uniqKey="Hecht J" first="Joel Randolph" last="Hecht">Joel Randolph Hecht</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Hurwitz, Herbert" sort="Hurwitz, Herbert" uniqKey="Hurwitz H" first="Herbert" last="Hurwitz">Herbert Hurwitz</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Diaz Rubio, Eduardo" sort="Diaz Rubio, Eduardo" uniqKey="Diaz Rubio E" first="Eduardo" last="Díaz-Rubio">Eduardo Díaz-Rubio</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Porschen, Rainer" sort="Porschen, Rainer" uniqKey="Porschen R" first="Rainer" last="Porschen">Rainer Porschen</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Tebbutt, Niall C" sort="Tebbutt, Niall C" uniqKey="Tebbutt N" first="Niall C." last="Tebbutt">Niall C. Tebbutt</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Fuchs, Charles" sort="Fuchs, Charles" uniqKey="Fuchs C" first="Charles" last="Fuchs">Charles Fuchs</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
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<author>
<name sortKey="Souglakos, John" sort="Souglakos, John" uniqKey="Souglakos J" first="John" last="Souglakos">John Souglakos</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
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<author>
<name sortKey="Falcone, Alfredo" sort="Falcone, Alfredo" uniqKey="Falcone A" first="Alfredo" last="Falcone">Alfredo Falcone</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Tournigand, Christophe" sort="Tournigand, Christophe" uniqKey="Tournigand C" first="Christophe" last="Tournigand">Christophe Tournigand</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Kabbinavar, Fairooz F" sort="Kabbinavar, Fairooz F" uniqKey="Kabbinavar F" first="Fairooz F." last="Kabbinavar">Fairooz F. Kabbinavar</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Heinemann, Volker" sort="Heinemann, Volker" uniqKey="Heinemann V" first="Volker" last="Heinemann">Volker Heinemann</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Van Cutsem, Eric" sort="Van Cutsem, Eric" uniqKey="Van Cutsem E" first="Eric" last="Van Cutsem">Eric Van Cutsem</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Bokemeyer, Carsten" sort="Bokemeyer, Carsten" uniqKey="Bokemeyer C" first="Carsten" last="Bokemeyer">Carsten Bokemeyer</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
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<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Buyse, Marc" sort="Buyse, Marc" uniqKey="Buyse M" first="Marc" last="Buyse">Marc Buyse</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
<wicri:regionArea>Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve</wicri:regionArea>
<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Sargent, Daniel J" sort="Sargent, Daniel J" uniqKey="Sargent D" first="Daniel J." last="Sargent">Daniel J. Sargent</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
<wicri:regionArea>Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France; John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Melbourne, Victoria, Australia; Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany; Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil; Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain; Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece; Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve</wicri:regionArea>
<wicri:noRegion>Louvain-la-Neuve</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Journal of Clinical Oncology</title>
<idno type="ISSN">0732-183X</idno>
<idno type="eISSN">1527-7755</idno>
<imprint>
<date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Angiogenesis Inhibitors (therapeutic use)</term>
<term>Antineoplastic Agents (therapeutic use)</term>
<term>Biomedical Research (methods)</term>
<term>Biomedical Research (statistics & numerical data)</term>
<term>Colorectal Neoplasms (drug therapy)</term>
<term>Colorectal Neoplasms (pathology)</term>
<term>Databases, Factual (statistics & numerical data)</term>
<term>Digestive System (drug effects)</term>
<term>Digestive System (pathology)</term>
<term>Disease-Free Survival</term>
<term>Humans</term>
<term>Middle Aged</term>
<term>Neoplasm Metastasis</term>
<term>Neoplasms (drug therapy)</term>
<term>Neoplasms (pathology)</term>
<term>Outcome Assessment (Health Care) (methods)</term>
<term>Outcome Assessment (Health Care) (statistics & numerical data)</term>
<term>Prognosis</term>
<term>Protein Kinase Inhibitors (therapeutic use)</term>
<term>Randomized Controlled Trials as Topic</term>
<term>Receptor, Epidermal Growth Factor (antagonists & inhibitors)</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Antinéoplasiques (usage thérapeutique)</term>
<term>Bases de données factuelles ()</term>
<term>Essais contrôlés randomisés comme sujet</term>
<term>Humains</term>
<term>Inhibiteurs de l'angiogenèse (usage thérapeutique)</term>
<term>Inhibiteurs de protéines kinases (usage thérapeutique)</term>
<term>Jeune adulte</term>
<term>Métastase tumorale</term>
<term>Pronostic</term>
<term>Recherche biomédicale ()</term>
<term>Récepteur du facteur de croissance épidermique (antagonistes et inhibiteurs)</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Survie sans rechute</term>
<term>Système digestif ()</term>
<term>Système digestif (anatomopathologie)</term>
<term>Tumeurs (anatomopathologie)</term>
<term>Tumeurs (traitement médicamenteux)</term>
<term>Tumeurs colorectales (anatomopathologie)</term>
<term>Tumeurs colorectales (traitement médicamenteux)</term>
<term>Évaluation de résultat (soins) ()</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en">
<term>Receptor, Epidermal Growth Factor</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en">
<term>Angiogenesis Inhibitors</term>
<term>Antineoplastic Agents</term>
<term>Protein Kinase Inhibitors</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr">
<term>Système digestif</term>
<term>Tumeurs</term>
<term>Tumeurs colorectales</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr">
<term>Récepteur du facteur de croissance épidermique</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Digestive System</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en">
<term>Colorectal Neoplasms</term>
<term>Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en">
<term>Biomedical Research</term>
<term>Outcome Assessment (Health Care)</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>Colorectal Neoplasms</term>
<term>Digestive System</term>
<term>Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="statistics & numerical data" xml:lang="en">
<term>Biomedical Research</term>
<term>Databases, Factual</term>
<term>Outcome Assessment (Health Care)</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr">
<term>Tumeurs</term>
<term>Tumeurs colorectales</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr">
<term>Antinéoplasiques</term>
<term>Inhibiteurs de l'angiogenèse</term>
<term>Inhibiteurs de protéines kinases</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Disease-Free Survival</term>
<term>Humans</term>
<term>Middle Aged</term>
<term>Neoplasm Metastasis</term>
<term>Prognosis</term>
<term>Randomized Controlled Trials as Topic</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Bases de données factuelles</term>
<term>Essais contrôlés randomisés comme sujet</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Métastase tumorale</term>
<term>Pronostic</term>
<term>Recherche biomédicale</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Survie sans rechute</term>
<term>Système digestif</term>
<term>Évaluation de résultat (soins)</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<sec>
<title>Purpose</title>
<p>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.</p>
</sec>
<sec>
<title>Methods</title>
<p>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
<italic>R</italic>
<sup>2</sup>
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.</p>
</sec>
<sec>
<title>Results</title>
<p>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 (
<italic>R</italic>
<sup>2</sup>
, 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>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.</p>
</sec>
</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Belgique</li>
</country>
</list>
<tree>
<country name="Belgique">
<noRegion>
<name sortKey="Shi, Qian" sort="Shi, Qian" uniqKey="Shi Q" first="Qian" last="Shi">Qian Shi</name>
</noRegion>
<name sortKey="Adams, Richard" sort="Adams, Richard" uniqKey="Adams R" first="Richard" last="Adams">Richard Adams</name>
<name sortKey="Bokemeyer, Carsten" sort="Bokemeyer, Carsten" uniqKey="Bokemeyer C" first="Carsten" last="Bokemeyer">Carsten Bokemeyer</name>
<name sortKey="Buyse, Marc" sort="Buyse, Marc" uniqKey="Buyse M" first="Marc" last="Buyse">Marc Buyse</name>
<name sortKey="Chibaudel, Benoist" sort="Chibaudel, Benoist" uniqKey="Chibaudel B" first="Benoist" last="Chibaudel">Benoist Chibaudel</name>
<name sortKey="De Gramont, Aimery" sort="De Gramont, Aimery" uniqKey="De Gramont A" first="Aimery" last="De Gramont">Aimery De Gramont</name>
<name sortKey="Diaz Rubio, Eduardo" sort="Diaz Rubio, Eduardo" uniqKey="Diaz Rubio E" first="Eduardo" last="Díaz-Rubio">Eduardo Díaz-Rubio</name>
<name sortKey="Douillard, Jean Yves" sort="Douillard, Jean Yves" uniqKey="Douillard J" first="Jean-Yves" last="Douillard">Jean-Yves Douillard</name>
<name sortKey="Falcone, Alfredo" sort="Falcone, Alfredo" uniqKey="Falcone A" first="Alfredo" last="Falcone">Alfredo Falcone</name>
<name sortKey="Fuchs, Charles" sort="Fuchs, Charles" uniqKey="Fuchs C" first="Charles" last="Fuchs">Charles Fuchs</name>
<name sortKey="Goldberg, Richard M" sort="Goldberg, Richard M" uniqKey="Goldberg R" first="Richard M." last="Goldberg">Richard M. Goldberg</name>
<name sortKey="Grothey, Axel" sort="Grothey, Axel" uniqKey="Grothey A" first="Axel" last="Grothey">Axel Grothey</name>
<name sortKey="Hecht, Joel Randolph" sort="Hecht, Joel Randolph" uniqKey="Hecht J" first="Joel Randolph" last="Hecht">Joel Randolph Hecht</name>
<name sortKey="Heinemann, Volker" sort="Heinemann, Volker" uniqKey="Heinemann V" first="Volker" last="Heinemann">Volker Heinemann</name>
<name sortKey="Hoff, Paulo M" sort="Hoff, Paulo M" uniqKey="Hoff P" first="Paulo M." last="Hoff">Paulo M. Hoff</name>
<name sortKey="Hurwitz, Herbert" sort="Hurwitz, Herbert" uniqKey="Hurwitz H" first="Herbert" last="Hurwitz">Herbert Hurwitz</name>
<name sortKey="Kabbinavar, Fairooz F" sort="Kabbinavar, Fairooz F" uniqKey="Kabbinavar F" first="Fairooz F." last="Kabbinavar">Fairooz F. Kabbinavar</name>
<name sortKey="Porschen, Rainer" sort="Porschen, Rainer" uniqKey="Porschen R" first="Rainer" last="Porschen">Rainer Porschen</name>
<name sortKey="Punt, Cornelis J A" sort="Punt, Cornelis J A" uniqKey="Punt C" first="Cornelis J. A." last="Punt">Cornelis J. A. Punt</name>
<name sortKey="Saltz, Leonard" sort="Saltz, Leonard" uniqKey="Saltz L" first="Leonard" last="Saltz">Leonard Saltz</name>
<name sortKey="Sargent, Daniel J" sort="Sargent, Daniel J" uniqKey="Sargent D" first="Daniel J." last="Sargent">Daniel J. Sargent</name>
<name sortKey="Schmoll, Hans Joachim" sort="Schmoll, Hans Joachim" uniqKey="Schmoll H" first="Hans-Joachim" last="Schmoll">Hans-Joachim Schmoll</name>
<name sortKey="Seymour, Matthew T" sort="Seymour, Matthew T" uniqKey="Seymour M" first="Matthew T." last="Seymour">Matthew T. Seymour</name>
<name sortKey="Souglakos, John" sort="Souglakos, John" uniqKey="Souglakos J" first="John" last="Souglakos">John Souglakos</name>
<name sortKey="Tebbutt, Niall C" sort="Tebbutt, Niall C" uniqKey="Tebbutt N" first="Niall C." last="Tebbutt">Niall C. Tebbutt</name>
<name sortKey="Tournigand, Christophe" sort="Tournigand, Christophe" uniqKey="Tournigand C" first="Christophe" last="Tournigand">Christophe Tournigand</name>
<name sortKey="Van Cutsem, Eric" sort="Van Cutsem, Eric" uniqKey="Van Cutsem E" first="Eric" last="Van Cutsem">Eric Van Cutsem</name>
<name sortKey="Zalcberg, John" sort="Zalcberg, John" uniqKey="Zalcberg J" first="John" last="Zalcberg">John Zalcberg</name>
</country>
</tree>
</affiliations>
</record>

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