Please use this identifier to cite or link to this item:
Title: Clinical Trial Endpoints in Metastatic Cancer: Using Individual Participant Data to Inform Future Trials Methodology.
Austin Authors: Goldberg, Richard M;Adams, Richard;Buyse, Marc;Eng, Cathy;Grothey, Axel;André, Thierry;Sobrero, Alberto F;Lichtman, Stuart M;Benson, Al B;Punt, Cornelis J A;Maughan, Tim;Burzykowski, Tomasz;Sommeijer, Dirkje;Saad, Everardo D;Shi, Qian;Coart, Elisabeth;Chibaudel, Benoist;Koopman, Miriam;Schmoll, Hans-Joachim;Yoshino, Takayuki;Taieb, Julien;Tebbutt, Niall C ;Zalcberg, John;Tabernero, Josep;Van Cutsem, Eric;Matheson, Alastair;de Gramont, Aimery
Affiliation: Monash University, School of Public Health, Australia..
West Virginia University Cancer Institute, Morgantown, WV, USA..
Austin Health
Cardiff University and Velindre UNHS Trust, UK..
International Drug Development Institute (IDDI), Louvain-la-Neuve, Belgium..
Vanderbilt-Ingram Cancer Center, Nashville, TN, USA..
West Cancer Center and Research Institute, Germantown, TN, USA..
Hôpital Saint Antoine, Paris, France..
Ospedale S. Martin, Genova, Italy..
Memorial Sloan Kettering Cancer Center, NY, USA..
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA..
University Medical Centre Utrecht, the Netherlands..
Gray Institute of Radiation Oncology and Biology, University of Oxford, UK..
University of Amsterdam Academic Medical Centre and Flevohospital, Almere, the Netherlands..
Dendrix Research, Sao Paulo, Brazil..
Mayo Clinic, Rochester, MN, USA..
Hôpital Franco-Britannique, Paris, France..
University Medical Centre Utrecht, the Netherlands..
Martin Luther University, Halle, Germany..
National Cancer Center Hospital East, Kashiwa, Japan..
Georges Pompidou European Hospital, Paris, France..
Vall d'Hebron Hospital Campus and Institute of Oncology (VHIO), Barcelona, Spain..
University Hospital Gasthuisberg, Leuven, Belgium..
Fondation ARCAD, Paris, France..
Hasselt University, Hasselt, Belgium..
Issue Date: 13-Jun-2022
Publication information: Journal of the National Cancer Institute 2022; 114(6): 819-828
Abstract: Meta-analysis based on individual participant data (IPD) is a powerful methodology for synthesizing evidence by combining information drawn from multiple trials. Hitherto, its principal application has been in questions of clinical management, but an increasingly important use is in clarifying trials methodology, for instance in the selection of endpoints, as discussed in this review. In oncology, the Aide et Recherche en Cancérologie Digestive (ARCAD) Metastatic Colorectal Cancer Database is a leader in the use of IPD-based meta-analysis in methodological research. The ARCAD database contains IPD from more than 38 000 patients enrolled in 46 studies and continues to collect phase III trial data. Here, we review the principal findings of the ARCAD project in respect of endpoint selection and examine their implications for cancer trials. Analysis of the database has confirmed that progression-free survival (PFS) is no longer a valid surrogate endpoint predictive of overall survival in the first-line treatment of colorectal cancer. Nonetheless, PFS remains an endpoint of choice for most first-line trials in metastatic colorectal cancer and other solid tumors. Only substantial PFS effects are likely to translate into clinically meaningful benefits, and accordingly, we advocate an oncology research model designed to identify highly effective treatments in carefully defined patient groups. We also review the use of the ARCAD database in assessing clinical response including novel response metrics and prognostic markers. These studies demonstrate the value of IPD as a tool for methodological studies and provide a reference point for the expansion of this approach within clinical cancer research.
DOI: 10.1093/jnci/djab218
ORCID: 0000-0003-0308-8223
PubMed URL: 34865086
PubMed URL:
Type: Journal Article
Appears in Collections:Journal articles

Show full item record

Page view(s)

checked on Jul 2, 2022

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.