Disease-free survival as surrogate for overall survival in esophageal cancer: An individual patient data meta-analysis of neoadjuvant chemotherapy and chemoradiotherapy
Year: 2025
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: BACKGROUND: The use of surrogate endpoints may expedite the reporting of study outcomes of clinical trials. The validity of disease-free survival (DFS) as a surrogate for overall survival (OS) in the neoadjuvant treatment of esophageal (E) or gastroesophageal junctional (GEJ) carcinomas remains uncertain. OBJECTIVE: To evaluate DFS as a surrogate end-point for OS in E/GEJ using the meta-analytical approach DESIGN, SETTING, AND PARTICIPANTS: individual patient data from an international meta-analysis on operable locally advanced E/GEJ, which including randomized trials comparing at least two of the neo-adjuvant treatment strategies: upfront surgery (S), chemotherapy followed by surgery (CS), and/or chemoradiotherapy followed by surgery (CRS). MAIN OUTCOMES AND MEASURES: Individual (Kendall's tau) and trial-level (R2) correlations between DFS and OS were estimated using a Clayton copula. RESULTS: DFS and OS data were available for a total of 4518 pts: 2222 pts included in CS vs S, 1908 pts in CRS vs S, and 388 in CS vs CRS comparisons. 3440 patients had a DFS event and 3303 patients died. Kendall's tau was 0.73 [95 % CI 0.71 - 0.75] and R2 trial-level correlation was 0.95 [0.84 - 0.99] for CS vs S, Kendall's tau was 0.76 [0.74 - 0.77] and R2 was 0.96 [0.87 - 0.99] for CRS vs S, Kendall's tau was 0.87 [0.78 - 0.92] and R2 was 0.93 [0.43 - 1] for CRS vs CS. In a multistate model, the median time in the recurrence state was shorter in older vs more recent trials: mean time of 10.8 [10.2 - 11.4] vs 16.5 months [15.4-17.6]. CONCLUSIONS AND RELEVANCE: DFS is a validated surrogate endpoint for OS in trials evaluating neoadjuvant chemotherapy or chemoradiotherapy in E/GEJ. DFS may be more useful as an endpoint when delays between recurrences and death become larger.
Source: European Journal of Cancer
Authors: Nicolas Cabrit, Maurice Cheugoua-Zanetsie, Jayne Tierney, Pierre Thirion, Matthew Nankivell, Kathryn Winter, Hong Yang, Bas Wijnhoven, Dewi Vernerey, B.Mark Smithers, Guillaume Piessen, Magnus Nilsson, Jurjen Boonstra, Marc Ychou, Simon Law, David Cunningham, Florent de Vathaire, Michael Stahl, Susan Urba, Michele Valmasoni, Danièle Williaume, Janine Thomas, Florian Lordick, Joel Tepper, Val Gebski, Bryan Burmeister, Xavier Paoletti, Johanna van Sandick, Jianhua Fu, Jean-Pierre Pignon, Michel Ducreux, Matthieu Faron, Stefan Michiels
Institutions: Inserm, Université Paris-Saclay, Centre de recherche en Epidémiologie et Santé des Populations, Institut Gustave Roussy, MRC Clinical Trials Unit at UCL, University College London, Trinity College Dublin, NRG Oncology, Sun Yat-sen University Cancer Center, Erasmus MC, Centre Hospitalier Universitaire de Besançon, The University of Queensland, Princess Alexandra Hospital, Centre National de la Recherche Scientifique, Université de Lille, CANTHER - Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers, Karolinska University Hospital, Karolinska Institutet, Leiden University Medical Center, University of Hong Kong, National Institute for Health and Care Research, Kliniken Essen-Mitte, University of Michigan, University of Padua, Centre Eugène Marquis, University Hospital Leipzig, Leipzig University, Institut Curie, The Netherlands Cancer Institute
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,270
Awards: G1370388735, G2490196836, G8750696687
OpenAlex ID: W4407260447