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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
International Drug Development Institute (IDDI), Louvain-la-Neuve, Belgium
Hasselt University, Hasselt, Belgium
Dendrix Research, Sao Paulo, Brazil
Hôpital Franco-Britannique, Paris, France
Fondation ARCAD, Paris, France
Austin Health
Cardiff University and Velindre UNHS Trust, UK
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, New York
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA
University Medical Centre Utrecht, Netherlands
Gray Institute of Radiation Oncology and Biology, University of Oxford, UK
University of Amsterdam Academic Medical Centre and Flevohospital, Almere, The Netherlands
Mayo Clinic, Rochester, MN, USA
International Drug Development Institute (IDDI), Louvain-la-Neuve, Belgium
Hôpital Franco-Britannique, Paris, France
University Medical Centre Utrecht, 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
Issue Date: 13-Jun-2022
Date: 2021-12-04
Publication information: Journal of the National Cancer Institute 2022; 114(6): 819-828
Abstract: Meta-analysis based upon 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 over 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
Journal: Journal of the National Cancer Institute
PubMed URL: 34865086
Type: Journal Article
Appears in Collections:Journal articles

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