Role of FGFR3 in bladder cancer: Treatment landscape and future challenges

FIGHT-101, a first-in-human study of potent and selective FGFR 1–3 inhibitor pemigatinib in pan-cancer patients with FGF/FGFR alterations and advanced malignancies

(2022) V. Subbiah et al.   ANNALS OF ONCOLOGY

Efficacy of derazantinib in intrahepatic cholangiocarcinoma patients with FGFR2 mutations or amplifications: Interim results from the phase 2 study FIDES-01.

(2022) Milind M. Javle et al.   JOURNAL OF CLINICAL ONCOLOGY

Futibatinib plus pembrolizumab in patients (pts) with advanced or metastatic urothelial carcinoma (mUC): Preliminary safety results from a phase 2 study.

(2022) Vadim S Koshkin et al.   JOURNAL OF CLINICAL ONCOLOGY

Validation and Characterization of FGFR2 Rearrangements in Cholangiocarcinoma with Comprehensive Genomic Profiling

(2022) Ian M. Silverman et al.   JOURNAL OF MOLECULAR DIAGNOSTICS

Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study

(2022) Arlene O Siefker-Radtke et al.   LANCET ONCOLOGY

Dual targeting of FGFR3 and ERBB3 enhances the efficacy of FGFR inhibitors in FGFR3 fusion-driven bladder cancer

(2022) Andrew J. Weickhardt et al.   BMC CANCER

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

(2021) Hyuna Sung et al.   CA-A CANCER JOURNAL FOR CLINICIANS

Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma

(2021) Thomas Powles et al.   NEW ENGLAND JOURNAL OF MEDICINE

Nuclear FGFR1 regulates gene transcription and promotes antiestrogen resistance in ER+ breast cancer

(2021) Alberto Servetto et al.   CLINICAL CANCER RESEARCH

TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors

(2021) Scott T. Tagawa et al.   JOURNAL OF CLINICAL ONCOLOGY

LBA27 Erdafitinib (ERDA) or ERDA plus cetrelimab (CET) for patients with metastatic or locally advanced urothelial carcinoma (mUC) and Fibroblast Growth Factor Receptor alterations (FGFRa): First phase (Ph) II results from the NORSE study

(2021) T.B. Powles et al.   ANNALS OF ONCOLOGY

European Association of Urology Guidelines on Non–muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma in Situ)

(2021) Marko Babjuk et al.   EUROPEAN UROLOGY

A phase 1 study of LY3076226, a fibroblast growth factor receptor 3 (FGFR3) antibody–drug conjugate, in patients with advanced or metastatic cancer

(2021) Christian Kollmannsberger et al.   INVESTIGATIONAL NEW DRUGS

Futibatinib, an irreversible FGFR1-4 inhibitor, in patients with advanced solid tumors harboring FGF/FGFR aberrations: a phase I dose-expansion study

(2021) Funda Meric-Bernstam et al.   Cancer Discovery

FGFR signaling and endocrine resistance in breast cancer: Challenges for the clinical development of FGFR inhibitors

(2021) Alberto Servetto et al.   BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER

Targetable Pathways in Advanced Bladder Cancer: FGFR Signaling

(2021) Jin-Fen Xiao et al.   Cancers

PROOF 302: A randomized, double-blind, placebo-controlled, phase III trial of infigratinib as adjuvant therapy in patients with invasive urothelial carcinoma harboring FGFR3 alterations.

(2020) Sumanta K. Pal et al.   JOURNAL OF CLINICAL ONCOLOGY

FIDES-02, a phase Ib/II study of derazantinib (DZB) as monotherapy and combination therapy with atezolizumab (A) in patients with surgically unresectable or metastaticurothelial cancer (UC) and FGFR genetic aberrations.

(2020) Arvind Chaudhry et al.   JOURNAL OF CLINICAL ONCOLOGY

Infigratinib and treatment response in advanced/unresectable or metastatic urothelial carcinoma in first-line and later-line treatment settings.

(2020) Yung Lyou et al.   JOURNAL OF CLINICAL ONCOLOGY

Safety and preliminary efficacy of rogaratinib in combination with atezolizumab in a phase Ib/II study (FORT-2) of first-line treatment in cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (UC) and FGFR mRNA overexpression.

(2020) Jonathan E. Rosenberg et al.   JOURNAL OF CLINICAL ONCOLOGY

FGFR expression, fusion and mutation as detected by NGS sequencing of DNA and RNA.

(2020) Ivan De Dios et al.   JOURNAL OF CLINICAL ONCOLOGY

Final results from the phase I study expansion cohort of the selective FGFR inhibitor Debio 1,347 in patients with solid tumors harboring an FGFR gene fusion.

(2020) James M. Cleary et al.   JOURNAL OF CLINICAL ONCOLOGY

INCB054828 (pemigatinib), a potent and selective inhibitor of fibroblast growth factor receptors 1, 2, and 3, displays activity against genetically defined tumor models

(2020) Phillip C. C. Liu et al.   PLoS One

Futibatinib is a novel irreversible FGFR 1-4 inhibitor that shows selective antitumor activity against FGFR-deregulated tumors

(2020) Hiroshi Sootome et al.   CANCER RESEARCH

Hyperphosphatemia Secondary to the Selective Fibroblast Growth Factor Receptor 1–3 Inhibitor Infigratinib (BGJ398) Is Associated with Antitumor Efficacy in Fibroblast Growth Factor Receptor 3–altered Advanced/Metastatic Urothelial Carcinoma

(2020) Yung Lyou et al.   EUROPEAN UROLOGY

Fibroblast Growth Factor Receptor (FGFR) Inhibitors in Urothelial Cancer

(2020) Rohan Garje et al.   ONCOLOGIST

Fibroblast growth factor receptors in cancer: genetic alterations, diagnostics, therapeutic targets and mechanisms of resistance

(2020) Melanie A. Krook et al.   BRITISH JOURNAL OF CANCER

Cancer statistics, 2019

(2019) Rebecca L. Siegel et al.   CA-A CANCER JOURNAL FOR CLINICIANS

Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer

(2019) Luigi Formisano et al.   Nature Communications

Rogaratinib: A potent and selective pan‐FGFR inhibitor with broad antitumor activity in FGFR‐overexpressing preclinical cancer models

(2019) Sylvia Grünewald et al.   INTERNATIONAL JOURNAL OF CANCER

A Phase I, Open-Label, Multicenter, Dose-escalation Study of the Oral Selective FGFR Inhibitor Debio 1347 in Patients with Advanced Solid Tumors Harboring FGFR Gene Alterations

(2019) Martin H. Voss et al.   CLINICAL CANCER RESEARCH

FUZE clinical trial: a phase 2 study of Debio 1347 in FGFR fusion-positive advanced solid tumors irrespectively of tumor histology.

(2019) David Michael Hyman et al.   JOURNAL OF CLINICAL ONCOLOGY

Baseline cfDNA characteristics and evolution of cfDNA profile during treatment with selective FGFR inhibitor TAS-120.

(2019) Tyler J. Moss et al.   JOURNAL OF CLINICAL ONCOLOGY

Interim analysis of the fierce-21 phase 2 (P2) study of vofatamab (B-701), a selective inhibitor of FGFR3, as salvage therapy in metastatic urothelial carcinoma (mUC).

(2019) Begona Mellado et al.   JOURNAL OF CLINICAL ONCOLOGY

Management of metastatic bladder cancer

(2019) Rosa Nadal et al.   CANCER TREATMENT REVIEWS

Fibroblast Growth Factor Receptor 3 Alterations and Response to PD-1/PD-L1 Blockade in Patients with Metastatic Urothelial Cancer

(2019) Li Wang et al.   EUROPEAN UROLOGY

Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma

(2019) Yohann Loriot et al.   NEW ENGLAND JOURNAL OF MEDICINE

A Consensus Molecular Classification of Muscle-invasive Bladder Cancer

(2019) Aurélie Kamoun et al.   EUROPEAN UROLOGY

917PClinical activity of vofatamab (V), an FGFR3 selective antibody in combination with pembrolizumab (P) in metastatic urothelial carcinoma (mUC), updated interim analysis of FIERCE-22

(2019) A O Siefker-Radtke et al.   ANNALS OF ONCOLOGY

Erdafitinib for the treatment of urothelial cancer

(2019) Laura Marandino et al.   Expert Review of Anticancer Therapy

Rogaratinib in patients with advanced cancers selected by FGFR mRNA expression: a phase 1 dose-escalation and dose-expansion study

(2019) Martin Schuler et al.   LANCET ONCOLOGY

Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial

(2018) Thomas Powles et al.   LANCET

Efficacy of BGJ398, a Fibroblast Growth Factor Receptor 1–3 Inhibitor, in Patients with Previously Treated Advanced Urothelial Carcinoma with FGFR3 Alterations

(2018) Sumanta K. Pal et al.   Cancer Discovery

Somatic FGFR3 Mutations Distinguish a Subgroup of Muscle-Invasive Bladder Cancers with Response to Neoadjuvant Chemotherapy

(2018) Zhao Yang et al.   EBioMedicine

FIERCE-21: Phase 1b/2 study of docetaxel + b-701, a selective inhibitor of FGFR3, in relapsed or refractory (R/R) metastatic urothelial carcinoma (mUCC).

(2018) Joaquim Bellmunt et al.   JOURNAL OF CLINICAL ONCOLOGY

900PInterim results of fight-201, a phase II, open-label, multicenter study of INCB054828 in patients (pts) with metastatic or surgically unresectable urothelial carcinoma (UC) harboring fibroblast growth factor (FGF)/FGF receptor (FGFR) genetic alterations (GA)

(2018) A Necchi et al.   ANNALS OF ONCOLOGY

920TiPErdafitinib compared with vinflunine or docetaxel or pembrolizumab in patients (pts) with metastatic or surgically unresectable (M/UR) urothelial carcinoma (UC) and selected fgfr gene alterations (FGFRalt): The phase III THOR study

(2018) Y Loriot et al.   ANNALS OF ONCOLOGY

Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma

(2018) Vincenzo Mazzaferro et al.   BRITISH JOURNAL OF CANCER

Forty years of cisplatin-based chemotherapy in muscle-invasive bladder cancer: are we understanding how, who and when?

(2018) Julian Schardt et al.   WORLD JOURNAL OF UROLOGY

A Functional Genetic Screen Identifies the Phosphoinositide 3-kinase Pathway as a Determinant of Resistance to Fibroblast Growth Factor Receptor Inhibitors in FGFR Mutant Urothelial Cell Carcinoma

(2017) Liqin Wang et al.   EUROPEAN UROLOGY

Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study

(2017) Lucia Nogova et al.   JOURNAL OF CLINICAL ONCOLOGY

Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial

(2017) Arjun V Balar et al.   LANCET

First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study

(2017) Arjun V Balar et al.   LANCET ONCOLOGY

Management of Muscle-Invasive Urothelial Cancer and the Emerging Role of Immunotherapy in Advanced Urothelial Cancer

(2017) Karthik V. Giridhar et al.   MAYO CLINIC PROCEEDINGS

Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor

(2017) Timothy P.S. Perera et al.   MOLECULAR CANCER THERAPEUTICS

Akt Activation Mediates Acquired Resistance to Fibroblast Growth Factor Receptor Inhibitor BGJ398

(2017) Jharna Datta et al.   MOLECULAR CANCER THERAPEUTICS

Fusions in solid tumours: diagnostic strategies, targeted therapy, and acquired resistance

(2017) Alison M. Schram et al.   Nature Reviews Clinical Oncology

AACR Project GENIE: Powering Precision Medicine through an International Consortium

(2017)   Cancer Discovery

A Phase II Trial of Dovitinib in BCG-Unresponsive Urothelial Carcinoma with FGFR3 Mutations or Overexpression: Hoosier Cancer Research Network Trial HCRN 12-157

(2016) Noah M. Hahn et al.   CLINICAL CANCER RESEARCH

FGFR inhibitors: Effects on cancer cells, tumor microenvironment and whole-body homeostasis (Review)

(2016) MASARU KATOH   INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE

Oncogenic Gene Fusion FGFR3-TACC3 Is Regulated by Tyrosine Phosphorylation

(2016) K. N. Nelson et al.   MOLECULAR CANCER RESEARCH

Inhibition of the fibroblast growth factor receptor (FGFR) pathway: the current landscape and barriers to clinical application

(2016) Young Kwang Chae et al.   Oncotarget

Effect of Thanatophoric Dysplasia Type I Mutations on FGFR3 Dimerization

(2015) Nuala Del Piccolo et al.   BIOPHYSICAL JOURNAL

Fibroblast growth factor receptor signaling in hereditary and neoplastic disease: biologic and clinical implications

(2015) Teresa Helsten et al.   CANCER AND METASTASIS REVIEWS

Detection, Characterization, and Inhibition of FGFR-TACC Fusions in IDH Wild-type Glioma

(2015) A. L. Di Stefano et al.   CLINICAL CANCER RESEARCH

The FGFR Landscape in Cancer: Analysis of 4,853 Tumors by Next-Generation Sequencing

(2015) T. Helsten et al.   CLINICAL CANCER RESEARCH

Functions of Fibroblast Growth Factor Receptors in cancer defined by novel translocations and mutations

(2015) Leandro H. Gallo et al.   CYTOKINE & GROWTH FACTOR REVIEWS

Update on Cardiovascular Safety of Tyrosine Kinase Inhibitors: With a Special Focus on QT Interval, Left Ventricular Dysfunction and Overall Risk/Benefit

(2015) Rashmi R. Shah et al.   DRUG SAFETY

The Effect of Mutations on Drug Sensitivity and Kinase Activity of Fibroblast Growth Factor Receptors: A Combined Experimental and Theoretical Study

(2015) Tom D. Bunney et al.   EBioMedicine

Phase 2 trial of dovitinib in patients with progressive FGFR3-mutated or FGFR3 wild-type advanced urothelial carcinoma

(2014) Matthew I. Milowsky et al.   EUROPEAN JOURNAL OF CANCER

Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012

(2014) Jacques Ferlay et al.   INTERNATIONAL JOURNAL OF CANCER

Dovitinib versus sorafenib for third-line targeted treatment of patients with metastatic renal cell carcinoma: an open-label, randomised phase 3 trial

(2014) Robert J Motzer et al.   LANCET ONCOLOGY

The Fibroblast Growth Factor Receptor Genetic Status as a Potential Predictor of the Sensitivity to CH5183284/Debio 1347, a Novel Selective FGFR Inhibitor

(2014) Y. Nakanishi et al.   MOLECULAR CANCER THERAPEUTICS

Comprehensive molecular characterization of urothelial bladder carcinoma

(2014)   NATURE

Acquired resistance to TKIs in solid tumours: learning from lung cancer

(2014) D. Ross Camidge et al.   Nature Reviews Clinical Oncology

Targeting FGFR with Dovitinib (TKI258): Preclinical and Clinical Data in Breast Cancer

(2013) F. Andre et al.   CLINICAL CANCER RESEARCH

The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma

(2013) Brittany C. Parker et al.   JOURNAL OF CLINICAL INVESTIGATION

Emergence of FGFR family gene fusions as therapeutic targets in a wide spectrum of solid tumours

(2013) Brittany C Parker et al.   JOURNAL OF PATHOLOGY

Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation

(2013) Guangwu Guo et al.   NATURE GENETICS

Exploring mechanisms of FGF signalling through the lens of structural biology

(2013) Regina Goetz et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Identification of Targetable FGFR Gene Fusions in Diverse Cancers

(2013) Yi-Mi Wu et al.   Cancer Discovery

Parallel RNA Interference Screens Identify EGFR Activation as an Escape Mechanism in FGFR3-Mutant Cancer

(2013) M. T. Herrera-Abreu et al.   Cancer Discovery

Identification of Fibroblast Growth Factor Receptor 3 (FGFR3) as a Protein Receptor for Botulinum Neurotoxin Serotype A (BoNT/A)

(2013) Birgitte P. S. Jacky et al.   PLoS Pathogens

Epidemiology and Risk Factors of Urothelial Bladder Cancer

(2012) Maximilian Burger et al.   EUROPEAN UROLOGY

Transforming Fusions of FGFR and TACC Genes in Human Glioblastoma

(2012) D. Singh et al.   SCIENCE

Treatment of Patients With Metastatic Urothelial Cancer “Unfit” for Cisplatin-Based Chemotherapy

(2011) Matthew D. Galsky et al.   JOURNAL OF CLINICAL ONCOLOGY

Discovery of 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), A Potent and Selective Inhibitor of the Fibroblast Growth Factor Receptor Family of Receptor Tyrosine Kinase

(2011) Vito Guagnano et al.   JOURNAL OF MEDICINAL CHEMISTRY

Small molecule FGF receptor inhibitors block FGFR-dependent urothelial carcinoma growth in vitro and in vivo

(2010) F R Lamont et al.   BRITISH JOURNAL OF CANCER

Biology of FGFRL1, the fifth fibroblast growth factor receptor

(2010) Beat Trueb   CELLULAR AND MOLECULAR LIFE SCIENCES

Fibroblast Growth Factors: Biology, Function, and Application for Tissue Regeneration

(2010) Ye-Rang Yun et al.   Journal of Tissue Engineering

Antibody-based targeting of FGFR3 in bladder carcinoma and t(4;14)-positive multiple myeloma in mice

(2009) Jing Qing et al.   JOURNAL OF CLINICAL INVESTIGATION

FGFR3-related dwarfism and cell signaling

(2008) Daisuke Harada et al.   JOURNAL OF BONE AND MINERAL METABOLISM

The cell surface receptor FGFRL1 forms constitutive dimers that promote cell adhesion

(2007) Thorsten Rieckmann et al.   EXPERIMENTAL CELL RESEARCH