2026-04-14T04:29:04Zhttps://recercat.cat/oai/request
oai:recercat.cat:2445/1957742025-12-05T13:12:43Zcom_2072_1057col_2072_478798col_2072_478916col_2072_478917
RECERCAT author Sternberg, Cora N. author Petrylak, Daniel P. author Bellmunt, Joaquim author Nishiyama, Hiroyuki author Necchi, Andrea author Gurney, Howard author Lee, Jae-Lyun author van der Heijden, Michiel S. author Rosenbaum, Eli author Penel, Nicolas author Pang, See-Tong author Li, Jian-Ri author García del Muro Solans, Xavier author Joly, Florens author Papai, Zsuzsanna author Bao, Weichao author Ellinghaus, Peter author Lu, Chengxing author Sierecki, Mitchell author Coppieters, Sabine author Nakajima, Keiko author Ishida, Tatiane Cristine author Quinn, David I. 2023-03-22T16:47:22Z2023-04-14T05:10:30Z2022-10-142023-03-22T16:47:22Z 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. (c) American Society of Clinical Oncology, 2022 info:eu-repo/semantics/openAccess Medicaments antineoplàstics Quimioteràpia Assaigs clínics de medicaments Càncer Antineoplastic agents Chemotherapy Drug testing Cancer 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 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion