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Clinical trial endpoints in metastatic cancer: using individual participant data to inform future trials methodology

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 and de Gramont, Aimery 2022. Clinical trial endpoints in metastatic cancer: using individual participant data to inform future trials methodology. Journal of the National Cancer Institute 114 (6) , pp. 819-828. 10.1093/jnci/djab218
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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Oxford University Press
ISSN: 0027-8874
Date of First Compliant Deposit: 3 February 2022
Date of Acceptance: 29 November 2021
Last Modified: 13 Jul 2022 13:11

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