Infigratinib in upper tract urothelial carcinoma versus urothelial carcinoma of the bladder and its association with comprehensive genomic profiling and/or cell‐free DNA results
Year: 2020
Type: article
Abstract: BACKGROUND: Infigratinib (BGJ398) is a potent and selective fibroblast grown factor receptor 1 to 3 (FGFR1-3) inhibitor with significant activity in patients with advanced or metastatic urothelial carcinoma bearing FGFR3 alterations. Given the distinct biologic characteristics of upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB), the authors examined whether infigratinib had varying activity in these settings. METHODS: Eligible patients had metastatic urothelial carcinoma with activating FGFR3 mutations and/or fusions. Comprehensive genomic profiling was performed on formalin-fixed, paraffin-embedded tissues. Blood was collected for cell-free DNA analysis using a 600-gene panel. Patients received infigratinib at a dose of 125 mg orally daily (3 weeks on/1 week off) until disease progression or intolerable toxicity occurred. The overall response rate (ORR; partial response [PR] plus complete response [CR]) and disease control rate (DCR; CR plus PR plus stable disease [SD]) were characterized. RESULTS: A total of 67 patients were enrolled; the majority (70.1%) had received ≥2 prior antineoplastic therapies. In 8 patients with UTUC, 1 CR and 3 PRs were observed (ORR, 50%); the remaining patients achieved a best response of SD (DCR, 100%). In patients with UCB, 13 PRs were observed (ORR, 22%), and 22 patients had a best response of SD (DCR, 59.3%). Notable differences in genomic alterations between patients with UTUC and those with UCB included higher frequencies of FGFR3-TACC3 fusions (12.5% vs 6.8%) and FGFR3 R248C mutations (50% vs 11.9%), and a lower frequency of FGFR3 S249C mutations (37.5% vs 59.3%). CONCLUSIONS: Differences in the cumulative genomic profile were observed between patients with UTUC and those with UCB in the current FGFR3-restricted experience, underscoring the distinct biology of these diseases. These results support a planned phase 3 adjuvant study predominantly performed in this population.
Source: Cancer
DOI: 10.1002/cncr.32806
Authors: Sumanta K. Pal, Dean Bajorin, Nazli Dizman, Jean Hoffman‐Censits, David I. Quinn, Daniel P. Petrylak, Matthew D. Galsky, Ulka Vaishampayan, Ugo De Giorgi, Sumati Gupta, Howard A. Burris, Harris S. Soifer, Gary Li, Hao Wang, Carl L. Dambkowski, Susan Moran, Siamak Daneshmand, Jonathan E. Rosenberg
Institutions: City Of Hope National Medical Center, City of Hope, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, Thomas Jefferson University, Sidney Kimmel Cancer Center, University of Southern California, USC Norris Comprehensive Cancer Center, Yale Cancer Center, Yale University, Mount Sinai Hospital, Tisch Cancer Institute, Wayne State University, The Barbara Ann Karmanos Cancer Institute, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, University of Utah, Huntsman Cancer Institute, Tennessee Oncology
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Celgene, Memorial Sloan-Kettering Cancer Center, Endocyte, Exelixis, Clovis Oncology, Five Prime Therapeutics, INOVIO Pharmaceuticals, Progenics Pharmaceuticals, HCA Healthcare, Mirati Therapeutics, Incyte, Advanced Accelerator Applications, UroGen Pharma, Eisai, Astellas Pharma, Ipsen, National Institutes of Health, Genentech, EMD Serono, Pharmacyclics, Foundation Medicine, National Cancer Institute, National Center for Advancing Translational Sciences
OpenAlex ID: W3012787501