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Title: Clinical Trial Endpoints in Metastatic Cancer: Using Individual Participant Data to Inform Future Trials Methodology
Authors: Goldberg, Richard M.
Adams, Richard
BUYSE, Marc 
Eng, Cathy
Grothey, Axel
Andre, Thierry
Sobrero, Alberto F.
Lichtman, Stuart M.
Benson, Al B.
Punt, Cornelis J. A.
Maughan, Tim
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
Issue Date: 2021
Source: JNCI-Journal of the National Cancer Institute,
Status: Early view
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 Cancerologie 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.
Notes: de Gramont, A (corresponding author), Hop Franco Britannique, 4 Rue Kleber, F-92300 Paris, France.
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ISSN: 0027-8874
e-ISSN: 1460-2105
DOI: 10.1093/jnci/djab218
ISI #: WOS:000765949500001
Rights: The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email:
Category: A1
Type: Journal Contribution
Appears in Collections:Research publications

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