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Title: | 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 |
Author: | 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. |
Keywords: | Medicaments antineoplàstics Quimioteràpia Assaigs clínics de medicaments Càncer Antineoplastic agents Chemotherapy Drug testing Cancer |
Issue Date: | 14-Oct-2022 |
Publisher: | American Society of Clinical Oncology |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1200/JCO.21.02303 |
It is part of: | Journal of Clinical Oncology, 2022, vol. 41, num. 3, p. 629-639 |
URI: | http://hdl.handle.net/2445/195774 |
Related resource: | https://doi.org/10.1200/JCO.21.02303 |
ISSN: | 0732-183X |
Appears in Collections: | Articles publicats en revistes (Ciències Clíniques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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