Miniatura

Fitxers

732754.pdf (320.25 KB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2022-10-14

Tots els drets reservats

Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/195774

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

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1200/JCO.21.02303

Resum

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.

Matèries

Medicaments antineoplàstics, Quimioteràpia, Assaigs clínics de medicaments, Càncer

Matèries (anglès)

Antineoplastic agents, Chemotherapy, Drug testing, Cancer

Citació

Col·leccions

Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

STERNBERG, Cora n., PETRYLAK, Daniel p., BELLMUNT, Joaquim, NISHIYAMA, Hiroyuki, NECCHI, Andrea, GURNEY, Howard, LEE, Jae-lyun, VAN DER HEIJDEN, Michiel s., ROSENBAUM, Eli, PENEL, Nicolas, PANG, See-tong, LI, Jian-ri, GARCÍA DEL MURO SOLANS, Xavier, JOLY, Florens, PAPAI, Zsuzsanna, BAO, Weichao, ELLINGHAUS, Peter, LU, Chengxing, SIERECKI, Mitchell, COPPIETERS, Sabine, NAKAJIMA, Keiko, ISHIDA, Tatiane cristine, QUINN, David i.. FORT-1: Phase II/III Study of Rogaratinib Versus Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Carcinoma Selected Based on FGFR1/3 mRNA Expression. _Journal of Clinical Oncology_. 2022. Vol. 41, núm. 3, pàgs. 629-639. [consulta: 26 de febrer de 2026]. ISSN: 0732-183X. [Disponible a: https://hdl.handle.net/2445/195774]

Exportar metadades

JSON - METS

Compartir registre