Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at : ckbsupport@genomenon.com

Ref Type

Journal Article

PMID

(36240478)

Authors

Sternberg CN, Petrylak DP, Bellmunt J, Nishiyama H, Necchi A, Gurney H, Lee JL, van der Heijden MS, Rosenbaum E, Penel N, Pang ST, Li JR, García Del Muro X, Joly F, Pápai Z, Bao W, Ellinghaus P, Lu C, Sierecki M, Coppieters S, Nakajima K, Ishida TC, Quinn DI

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.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of clinical oncology : official journal of the American Society of Clinical Oncology	41	3	2023 Jan 20	629-639	J Clin Oncol

URL

Abstract Text

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.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.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.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.

Filtering

Case insensitive filtering will display rows if any text in any cell matches the filter term
Use simple literal full or partial string matches
Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
FGFR1 over exp	transitional cell carcinoma	no benefit	Rogaratinib	Phase II	Actionable	In a Phase II trial (FORT-1), Rogaratinib (BAY 1163877) treatment did not result in improved outcomes compared to chemotherapy in advanced or metastatic urothelial carcinoma patients with FGFR1 or FGFR3 overexpression, with similar median overall survival (8.3 mo vs 9.8 mo), median progression-free survival (2.7 mo vs. 3.2 mo), and objective response rate (20.7% (18/87) vs 19.3% (17/88)), failing to meet the predetermined criteria for continuation to Phase III (PMID: 36240478; NCT03410693).	36240478
FGFR3 over exp	transitional cell carcinoma	no benefit	Rogaratinib	Phase II	Actionable	In a Phase II trial (FORT-1), Rogaratinib (BAY 1163877) treatment did not result in improved outcomes compared to chemotherapy in advanced or metastatic urothelial carcinoma patients with FGFR1 or FGFR3 overexpression, with similar median overall survival (8.3 mo vs 9.8 mo), median progression-free survival (2.7 mo vs. 3.2 mo), and objective response rate (20.7% (18/87) vs 19.3% (17/88)), failing to meet the predetermined criteria for continuation to Phase III (PMID: 36240478; NCT03410693).	36240478
FGFR3 act mut FGFR3 over exp	transitional cell carcinoma	predicted - sensitive	Rogaratinib	Phase II	Actionable	In a Phase II trial (FORT-1), Rogaratinib (BAY 1163877) treatment resulted in a higher objective response rate of 52.4% (11/21) compared to 26.7% (4/15) with chemotherapy in advanced or metastatic urothelial carcinoma patients with FGFR3 overexpression and an FGFR3 alteration (including FGFR3 G370C, FGFR3 R248C, FGFR3 S249C, FGFR3 Y373C, FGFR3-TACC3v1, and FGFR3-TACC3v3) (PMID: 36240478; NCT03410693).	36240478