Enrichment of FGFR3-TACC3 Fusions in Patients With Bladder Cancer Who Are Young, Asian, or Have Never Smoked.

Purpose: FGFR3-TACC3 (fibroblast growth factor receptor 3-transforming acidic coiled coil-containing protein 3) fusions have recently been identified as driver mutations that lead to the activation of FGFR3 in bladder cancer and other tumor types and are associated with sensitivity to tyrosine kinase inhibitors. We examined the clinical and molecular characteristics of patients with FGFR3-TACC3 fusions and hypothesized that they are enriched in a subset of patients with bladder cancer.
Materials and Methods: We correlated somatic FGFR3-TACC3 fusions with clinical and molecular features in two cohorts of patients with bladder cancer. The first cohort consisted of the muscle-invasive bladder cancer (MIBC) data set (n = 412) from The Cancer Genome Atlas. The second cohort consisted of patients with MIBC or high-grade non-MIBC at the Dana-Farber Cancer Institute that had targeted capture sequencing of a selected panel of cancer genes (n = 356). All statistical tests were two sided. The clinical response of one patient with FGFR3-TACC3 bladder cancer to an FGFR3 inhibitor was investigated.
Results: Overall, 751 patients with high-grade bladder cancer without FGFR3-TACC3 fusions and 17 with FGFR3-TACC3 fusions were identified in the pooled analysis of the data sets from The Cancer Genome Atlas and the Dana-Farber Cancer Institute. FGFR3-TACC3 fusions were enriched in patients age ≤ 50 years versus age 51 to 65 years versus those older than 65 years (pooled, P = .002), and were observed in four (12%) of 33 patients age ≤ 50 years in the pooled analysis. Similarly, FGFR3-TACC3 fusions were significantly more common in Asians (13%) compared with African Americans (4%) and whites (2%; pooled, P < .001), as well as in never smokers (5.6%) compared with ever smokers (1.1%; pooled, P < .001). One patient with the fusion who was treated with an FGFR3 inhibitor achieved complete remission for 10 months.
Conclusion: Clinical testing to identify FGFR3 fusions should be prioritized for patients with bladder cancer who are younger, never smokers, and/or Asian.
Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Amin H. NassarNo relationship to discloseKevin LundgrenNo relationship to discloseMark PomerantzHonoraria: BayerEliezer Van AllenStock and Other Ownership Interests: Synapse, Tango Therapeutics, Genome Medical Consulting or Advisory Role: Synapse, Roche, Third Rock Ventures, Takeda, Novartis, Genome Medical, InVitae Speakers' Bureau: Illumina Research Funding: Bristol-Myers Squibb, NovartisLauren HarshmanConsulting or Advisory Role: Medivation, Astellas Pharma, Pfizer, Genentech, Theragene, KEW, Corvus Pharmaceuticals, Merck, Exelixis, Bayer Research Funding: Medivation, Astellas Pharma (Inst), Bayer (Inst), Sotio (Inst), Genentech (Inst), Dendreon (Inst), Bristol-Myers Squibb (Inst), Takeda (Inst), Merck (Inst), Janssen Oncology (Inst), Pfizer (Inst) Travel, Accommodations, Expenses: BayerAtish D. ChoudhuryEmployment: LeMaitre Vascular (I) Honoraria: Bayer, Astellas Pharma Research Funding: Janssen Pharmaceuticals (Inst)Mark A. PrestonNo relationship to discloseGraeme S. SteeleNo relationship to discloseKent W. MouwConsulting or Advisory Role: Pfizer, EMD SeronoXiao X. WeiNo relationship to discloseBradley A. McGregorConsulting or Advisory Role: Bayer, Seattle Genetics, Astellas Pharma, Exelixis, AstraZeneca, Genentech, NextarToni K. ChoueiriHonoraria: National Comprehensive Cancer Network, UpToDate Consulting or Advisory Role: Pfizer, Bayer, Novartis, GlaxoSmithKline, Merck, Bristol-Myers Squibb, Genentech, Eisai, Foundation Medicine, Cerulean Pharma, AstraZeneca, Peloton Therapeutics, Exelixis, Prometheus Laboratories, Alligent, Ipsen, Corvus Pharmaceuticals Research Funding: Pfizer (Inst), Novartis (Inst), Merck (Inst), Exelixis (Inst), TRACON Pharma (Inst), GlaxoSmithKline (Inst), Bristol-Myers Squibb (Inst), AstraZeneca (Inst), Peloton Therapeutics (Inst), Genentech (Inst), Celldex (Inst), Agensys (Inst), Eisai (Inst)Joaquim BellmuntHonoraria: UpToDate Consulting or Advisory Role: Pierre Fabre, Astellas Pharma, Pfizer, Merck, Genentech, Novartis, AstraZeneca, MedImmune, Bristol-Myers Squibb Research Funding: Millennium Pharmaceuticals (Inst), Sanofi (Inst) Travel, Accommodations, Expenses: Pfizer, MSD OncologyDavid J. KwiatkowskiConsulting or Advisory Role: AstraZeneca, Genentech Research Funding: AADiGuru P. SonpavdeHonoraria: UpToDate Consulting or Advisory Role: Bayer, Genentech, Sanofi, Merck, Novartis, Pfizer, Argos Therapeutics, Agensys, Eisai, AstraZeneca, Janssen Pharmaceuticals, Amgen, Bristol-Myers Squibb, Exelixis Speakers' Bureau: Clinical Care Options, National Comprehensive Cancer Network, Physician Education Resource, Onclive, Research to Practice Research Funding: Onyx Pharmaceuticals (Inst), Bayer (Inst), Boehringer Ingelheim (Inst), Celgene (Inst), Merck (Inst), Pfizer (Inst) Other Relationship: Boehringer Ingelheim, AstraZeneca
(© 2018 by American Society of Clinical Oncology.)