Reference Detail

Ref Type

Journal Article

PMID

(37980453)

Authors

Saridogan T, Akcakanat A, Zhao M, Evans KW, Yuca E, Scott S, Kirby BP, Zheng X, Ha MJ, Chen H, Ng PKS, DiPeri TP, Mills GB, Rodon Ahnert J, Damodaran S, Meric-Bernstam F

Title

Efficacy of futibatinib, an irreversible fibroblast growth factor receptor inhibitor, in FGFR-altered breast cancer.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Scientific reports	13	1	2023 Nov 18	20223	Sci Rep

URL

Abstract Text

Several alterations in fibroblast growth factor receptor (FGFR) genes have been found in breast cancer; however, they have not been well characterized as therapeutic targets. Futibatinib (TAS-120; Taiho) is a novel, selective, pan-FGFR inhibitor that inhibits FGFR1-4 at nanomolar concentrations. We sought to determine futibatinib's efficacy in breast cancer models. Nine breast cancer patient-derived xenografts (PDXs) with various FGFR1-4 alterations and expression levels were treated with futibatinib. Antitumor efficacy was evaluated by change in tumor volume and time to tumor doubling. Alterations indicating sensitization to futibatinib in vivo were further characterized in vitro. FGFR gene expression between patient tumors and matching PDXs was significantly correlated; however, overall PDXs had higher FGFR3-4 expression. Futibatinib inhibited tumor growth in 3 of 9 PDXs, with tumor stabilization in an FGFR2-amplified model and prolonged regression (> 110 days) in an FGFR2 Y375C mutant/amplified model. FGFR2 overexpression and, to a greater extent, FGFR2 Y375C expression in MCF10A cells enhanced cell growth and sensitivity to futibatinib. Per institutional and public databases, FGFR2 mutations and amplifications had a population frequency of 1.1%-2.6% and 1.5%-2.5%, respectively, in breast cancer patients. FGFR2 alterations in breast cancer may represent infrequent but highly promising targets for futibatinib.

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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
FGFR2 Y375C FGFR2 amp	triple-receptor negative breast cancer	sensitive	Futibatinib	Preclinical - Pdx	Actionable	In a preclinical study, Lytgobi (furibatinib) inhibited viability of cells derived from a patient-derived xenograft (PDX) model of FGFR2-amplified triple-negative breast cancer harboring FGFR2 Y375C in culture and induced tumor regression and improved survival in the patient-derived xenograft (PDX) model (PMID: 37980453).	37980453
FGFR2 Y375C	breast cancer	sensitive	Erdafitinib	Preclinical - Cell culture	Actionable	In a preclinical study, Balversa (erdafitinib) inhibited viability of breast epithelial cells expressing FGFR2 Y375C in culture (PMID: 37980453).	37980453
FGFR2 Y375C	breast cancer	sensitive	Fexagratinib	Preclinical - Cell culture	Actionable	In a preclinical study, AZD4547 inhibited viability of breast epithelial cells expressing FGFR2 Y375C in culture (PMID: 37980453).	37980453
FGFR2 Y375C	breast cancer	sensitive	Pemigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Pemazyre (pemigatinib) inhibited viability of breast epithelial cells expressing FGFR2 Y375C in culture (PMID: 37980453).	37980453
FGFR2 Y375C FGFR2 amp	triple-receptor negative breast cancer	sensitive	Pemigatinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, Pemazyre (pemigatinib) inhibited viability of cells derived from a patient-derived xenograft (PDX) model of FGFR2-amplified triple-negative breast cancer harboring FGFR2 Y375C in culture (PMID: 37980453).	37980453
FGFR2 Y375C	breast cancer	sensitive	Futibatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lytgobi (futibatinib) inhibited Fgfr2 signaling and viability in breast epithelial cells expressing FGFR2 Y375C in culture (PMID: 37980453).	37980453
FGFR2 Y375C	cholangiocarcinoma	sensitive	Futibatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lytgobi (futibatinib) inhibited viability of a cholangiocyte cell line harboring FGFR2 Y375C in culture (PMID: 37980453).	37980453
FGFR2 Y375C	breast cancer	sensitive	Dovitinib	Preclinical - Cell culture	Actionable	In a preclinical study, Dovitinib (TKI258) inhibited viability of breast epithelial cells expressing FGFR2 Y375C in culture (PMID: 37980453).	37980453
FGFR2 amp	breast cancer	sensitive	Futibatinib	Preclinical - Pdx	Actionable	In a preclinical study, Lytgoi (futibatinib) inhibited tumor growth and improved survival in a patient-derived xenograft (PDX) model of FGFR2-amplified breast cancer (PMID: 37980453).	37980453