Thirty-Month Complete Response as a Surrogate ...
Type de document :
Article dans une revue scientifique
DOI :
PMID :
URL permanente :
Titre :
Thirty-Month Complete Response as a Surrogate End Point in First-Line Follicular Lymphoma Therapy: An Individual Patient-Level Analysis of Multiple Randomized Trials
Auteur(s) :
Shi, Qian [Auteur]
Flowers Christopher, R [Auteur]
Hiddemann, Wolfgang [Auteur]
Marcus, Robert [Auteur]
Herold, Michael [Auteur]
Hagenbeek, Anton [Auteur]
Kimby, Eva [Auteur]
Hochster, Howard [Auteur]
Vitolo, Umberto [Auteur]
Peterson Bruce, A [Auteur]
Gyan, Emmanuel [Auteur]
Ghielmini, Michele [Auteur]
Nielsen, Tina [Auteur]
De Bedout, Sabine [Auteur]
Fu, Tommy [Auteur]
Valente, Nancy [Auteur]
Fowler, Nathan [Auteur]
Hoster, Eva [Auteur]
Ladetto, Marco [Auteur]
Morschhauser, Franck [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Zucca, Emanuele [Auteur]
Salles, Gilles [Auteur]
Sargent Daniel, J [Auteur]
Flowers Christopher, R [Auteur]
Hiddemann, Wolfgang [Auteur]
Marcus, Robert [Auteur]
Herold, Michael [Auteur]
Hagenbeek, Anton [Auteur]
Kimby, Eva [Auteur]
Hochster, Howard [Auteur]
Vitolo, Umberto [Auteur]
Peterson Bruce, A [Auteur]
Gyan, Emmanuel [Auteur]
Ghielmini, Michele [Auteur]
Nielsen, Tina [Auteur]
De Bedout, Sabine [Auteur]
Fu, Tommy [Auteur]
Valente, Nancy [Auteur]
Fowler, Nathan [Auteur]
Hoster, Eva [Auteur]
Ladetto, Marco [Auteur]
Morschhauser, Franck [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Zucca, Emanuele [Auteur]
Salles, Gilles [Auteur]
Sargent Daniel, J [Auteur]
Titre de la revue :
Journal of clinical oncology
Nom court de la revue :
J. Clin. Oncol.
Numéro :
35
Pagination :
552
Date de publication :
2017
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Purpose Follicular lymphoma (FL) is an indolent cancer, with effective but rarely curative treatment options. As a standard study end point for first-line FL therapy, progression-free survival (PFS) requires extended ...
Lire la suite >Purpose Follicular lymphoma (FL) is an indolent cancer, with effective but rarely curative treatment options. As a standard study end point for first-line FL therapy, progression-free survival (PFS) requires extended follow-up (median PFS, > 7 years). To provide patients with earlier access to newer therapies, an earlier end point to expedite clinical trials is needed. Our objective was to formally assess the complete response rate at 30 months (CR30) after initiation of induction therapy as a potential surrogate end point for PFS in first-line FL therapy. Patients and Methods We analyzed individual patient data from 13 randomized multicenter trials of induction and maintenance regimens in first-line FL therapy published after 1990 and with sufficient data to evaluate whether CR30 could predict treatment effects on PFS. Correlation of the CR30 odds ratio with the PFS hazard ratio was evaluated by both linear regression (R2WLS) and bivariate copula (R2Copula) models. Prespecified criteria for surrogacy required either R2WLS or R2Copula ≥ 0.80, with a lower-bound 95% CI > 0.60. Results Data from eight induction and five maintenance randomized trials in 3,837 evaluable patients were analyzed. The prespecified surrogacy threshold was met, with an R2WLS of 0.88 (95% CI, 0.77 to 0.96) and an R2Copula of 0.86 (95% CI, 0.72 to 1.00). Multiple sensitivity and supplemental analyses supported the robustness of the findings. A minimum 11% absolute improvement in CR30 from a 50% control rate predicted a significant treatment effect on PFS (hazard ratio, 0.69). Conclusion This large, prospective, pooled analysis of randomized chemotherapy, immunotherapy, and chemoimmunotherapy trials demonstrates that CR30 is a surrogate end point for PFS in first-line FL treatment trials. Use of this end point may expedite therapeutic development with the intent of bringing novel therapies to this patient population years before PFS results are mature.Lire moins >
Lire la suite >Purpose Follicular lymphoma (FL) is an indolent cancer, with effective but rarely curative treatment options. As a standard study end point for first-line FL therapy, progression-free survival (PFS) requires extended follow-up (median PFS, > 7 years). To provide patients with earlier access to newer therapies, an earlier end point to expedite clinical trials is needed. Our objective was to formally assess the complete response rate at 30 months (CR30) after initiation of induction therapy as a potential surrogate end point for PFS in first-line FL therapy. Patients and Methods We analyzed individual patient data from 13 randomized multicenter trials of induction and maintenance regimens in first-line FL therapy published after 1990 and with sufficient data to evaluate whether CR30 could predict treatment effects on PFS. Correlation of the CR30 odds ratio with the PFS hazard ratio was evaluated by both linear regression (R2WLS) and bivariate copula (R2Copula) models. Prespecified criteria for surrogacy required either R2WLS or R2Copula ≥ 0.80, with a lower-bound 95% CI > 0.60. Results Data from eight induction and five maintenance randomized trials in 3,837 evaluable patients were analyzed. The prespecified surrogacy threshold was met, with an R2WLS of 0.88 (95% CI, 0.77 to 0.96) and an R2Copula of 0.86 (95% CI, 0.72 to 1.00). Multiple sensitivity and supplemental analyses supported the robustness of the findings. A minimum 11% absolute improvement in CR30 from a 50% control rate predicted a significant treatment effect on PFS (hazard ratio, 0.69). Conclusion This large, prospective, pooled analysis of randomized chemotherapy, immunotherapy, and chemoimmunotherapy trials demonstrates that CR30 is a surrogate end point for PFS in first-line FL treatment trials. Use of this end point may expedite therapeutic development with the intent of bringing novel therapies to this patient population years before PFS results are mature.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
CHU Lille
CHU Lille
Collections :
Équipe(s) de recherche :
Innovation/évaluation des médicaments injectables
Date de dépôt :
2019-02-26T17:07:18Z