Surrogate end points for overall survival and local control in neoadjuvant rectal cancer trials: statistical evaluation based on the FFCD 9203 trial.
Fiche publication
Date publication
mars 2010
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BEDENNE Laurent, Pr BOUCHE Olivier, Pr CONROY Thierry
Tous les auteurs :
Methy N, Bedenne L, Conroy T, Bouche O, Chapet O, Ducreux M, Gerard JP, Bonnetain F
Lien Pubmed
Résumé
BACKGROUND: In resectable rectal cancer trials, pathological parameters are early preoperative treatment efficacy measures. Their validation as surrogate end points for long-term clinical outcomes would allow to reduce trial duration. The aim was to evaluate potential surrogates for overall survival (OS) and local control (LC) in preoperative T3/T4 rectal cancer trials. Candidate variables included ypT and ypN stages, T downstaging, tumor regression grade (TRG), and circumferential resection margin (CRM) status. PATIENTS AND METHODS: In the Federation Francophone de Cancerologie Digestive (FFCD) 9203 trial, 742 eligible patients were randomly assigned to receive preoperative radiotherapy with or without concurrent chemotherapy. Surrogacy was evaluated using Prentice criteria and the proportion of treatment effect (PTE) explained by each potential surrogate. RESULTS: None of the candidate surrogates fulfilled all Prentice criteria. Data analyses did not provide interpretable PTE measures for OS. Regarding LC, the highest PTE was reached by TRG, which explained 12% of the effect on local recurrence. This proportion may not exceed 41% [95% confidence interval (CI) -1% to 41%]. PTE explained by the CRM status was associated with a wide uncertainty (95% CI -81% to 105%), which does not exclude a potentially high degree of surrogacy. CONCLUSION: In the FFCD 9203 trial, pathological parameters were not surrogate for OS or LC.
Référence
Ann Oncol. 2010 Mar;21(3):518-24