title: [Not Available].
abstract: HOW A BIOMARKER CAN BECOME AN ACCEPTABLE SUBSTITUTION CRITERIA ?: Numerous biomarkers of the treatment activity are now available as a result of the fascinating progresses in biology and biotechnology. Together with the rapidly growing understanding of the mechanisms of action of new agents, these biomarkers provide promising tools to evaluate early the effect of treatments against cancer. It is tempting to use these new markers of activity as primary endpoints to evaluate new treatments in the context of randomized clinical trials. Nevertheless, a mandatory preliminary step is to demonstrate that the two endpoints carry the same information in order to validate whether the biomarker is a surrogate of the final endpoint. We illustrate on several examples in prostate, gastric and early breast cancer that it is important to distinguish two levels of information: the individual level that allows to monitor a patient to anticipate treatment failure, and the trial level that enables to predict the treatment effect on the final endpoint based on the treatment effect measured on the surrogate endpoint. In several cases, the formal validation turned out to be disappointing despite strong biological rational.
authors: Gustave Roussy ; Service de biostatistique et d'épidémiologie ; Inserm U1018 CESP, Université Paris-Sud, Université Paris-Saclay, Equipe OncoStat; 114 rue Ed. Vaillant 94805 Villejuif cedex. Electronic address: xavier.paoletti@gustaveroussy.fr.
authors: Xavier
authors: X
authors: Paoletti
authors: Gustave Roussy ; Service de biostatistique et d'épidémiologie ; Inserm U1018 CESP, Université Paris-Sud, Université Paris-Saclay, Equipe OncoStat; 114 rue Ed. Vaillant 94805 Villejuif cedex.
authors: Federico
authors: F
authors: Rotolo
authors: Gustave Roussy ; Service de biostatistique et d'épidémiologie ; Inserm U1018 CESP, Université Paris-Sud, Université Paris-Saclay, Equipe OncoStat; 114 rue Ed. Vaillant 94805 Villejuif cedex.
authors: Stefan
authors: S
authors: Michiels
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D009360:Neoplastic Cells, Circulating; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy*; D013274:Stomach Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor
keywords: Biomarker,pathological; Biomarqueur; Cellules tumorales; Circulating tumor cells; Overall survival; Réponse pathologique; Surrogate; Survie globale; circulantes; response