Titre :

FORT-1: Phase II/III Study of Rogaratinib Versus Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Carcinoma Selected Based on <i>FGFR1</i>/ <i>3</i> mRNA Expression.

Auteur(s) :

Sternberg, Cora N. [Auteur]
Sandra and Edward Meyer Cancer Center [New-York]
Petrylak, Daniel P. [Auteur]
Yale University [New Haven]
Bellmunt, Joaquim [Auteur]
IMIM-Hospital del Mar
Harvard Medical School [Boston] [HMS]
Nishiyama, Hiroyuki [Auteur]
Université de Tsukuba = University of Tsukuba
Necchi, Andrea [Auteur]
Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] [UniSR]
Gurney, Howard [Auteur]
Macquarie University
Lee, Jae-Lyun [Auteur]
University of Ulsan
Van Der Heijden, Michiel S. [Auteur]
Netherlands Cancer Institute [NKI]
Rosenbaum, Eli [Auteur]
Penel, Nicolas [Auteur]
Service d'oncologie médicale (CHRU Lille)
METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694
Pang, See-Tong [Auteur]
Chang Gung Memorial Hospital [Taipei] [CGMH]
Li, Jian-Ri [Auteur]
Tunghai University [Taichung]
García Del Muro, Xavier [Auteur]

Joly, Florence [Auteur]
Service de recherche clinique [Centre François Baclesse]
Pápai, Zsuzsanna [Auteur]
National Institute of Oncology [Budapest, Hungary]
Bao, Weichao [Auteur]
Bayer HealthCare Pharmaceuticals Inc [Whippany]
Ellinghaus, Peter [Auteur]
Bayer Pharma AG [Berlin]
Lu, Chengxing [Auteur]
Bayer HealthCare Pharmaceuticals Inc [Whippany]
Sierecki, Mitchell [Auteur]
Bayer HealthCare Pharmaceuticals Inc [Whippany]
Coppieters, Sabine [Auteur]
Nakajima, Keiko [Auteur]
Bayer HealthCare Pharmaceuticals Inc [Whippany]
Ishida, Tatiane Cristine [Auteur]
Bayer HealthCare Pharmaceuticals Inc [Whippany]
Quinn, David I. [Auteur]
School of Medicine [Los Angeles]

Titre de la revue :

Journal of Clinical Oncology

Nom court de la revue :

J Clin Oncol

Pagination :

JCO2102303

Date de publication :

2022-10-16

ISSN :

1527-7755

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

PURPOSE Rogaratinib, an oral pan-fibroblast growth factor receptor (FGFR1-4) inhibitor, showed promising phase I efficacy and safety in patients with advanced urothelial carcinoma (UC) with FGFR1-3 mRNA overexpression. ...
Lire la suite >PURPOSE Rogaratinib, an oral pan-fibroblast growth factor receptor (FGFR1-4) inhibitor, showed promising phase I efficacy and safety in patients with advanced urothelial carcinoma (UC) with FGFR1-3 mRNA overexpression. We assessed rogaratinib efficacy and safety versus chemotherapy in patients with FGFR mRNA-positive advanced/metastatic UC previously treated with platinum chemotherapy. METHODS FORT-1 (ClinicalTrials.gov identifier: NCT03410693) was a phase II/III, randomized, open-label trial. Patients with FGFR1/3 mRNA-positive locally advanced or metastatic UC with ≥ 1 prior platinum-containing regimen were randomly assigned (1:1) to rogaratinib (800 mg orally twice daily, 3-week cycles; n = 87) or chemotherapy (docetaxel 75 mg/m2, paclitaxel 175 mg/m2, or vinflunine 320 mg/m2 intravenously once every 3 weeks; n = 88). The primary end point was overall survival, with objective response rate (ORR) analysis planned following phase II accrual. Because of comparable efficacy between treatments, enrollment was stopped before progression to phase III; a full interim analysis of phase II was completed. RESULTS ORRs were 20.7% (rogaratinib, 18/87; 95% CI, 12.7 to 30.7) and 19.3% (chemotherapy, 17/88; 95% CI, 11.7 to 29.1). Median overall survival was 8.3 months (95% CI, 6.5 to not estimable) and 9.8 months (95% CI, 6.8 to not estimable; hazard ratio, 1.11; 95% CI, 0.71 to 1.72; P = .67). Grade 3/4 events occurred in 37 (43.0%)/4 (4.7%) patients and 32 (39.0%)/15 (18.3%), respectively. No rogaratinib-related deaths occurred. Exploratory analysis of patients with FGFR3 DNA alterations showed ORRs of 52.4% (11/21; 95% CI, 29.8 to 74.3) for rogaratinib and 26.7% (4/15; 95% CI, 7.8 to 55.1) for chemotherapy. CONCLUSION To our knowledge, these are the first data to compare FGFR-directed therapy with chemotherapy in patients with FGFR-altered UC, showing comparable efficacy and manageable safety. Exploratory testing suggested FGFR3 DNA alterations in association with FGFR1/3 mRNA overexpression may be better predictors of rogaratinib response.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CHU Lille

Collections :

• METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694

Date de dépôt :

2023-11-15T03:11:20Z
2023-12-18T12:38:43Z