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.
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.
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%).
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.
Cancer. 2020 Mar 24 [Epub]
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
Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California., Genitourinary Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Departments of Medical Oncology and Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., University of Southern California Norris Comprehensive Cancer Center Keck School of Medicine at USC, Los Angeles, California., Department of Medicine, Division of Oncology, Yale School of Medicine, New Haven, Connecticut., Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, The Mount Sinai Hospital, New York, New York., Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan., Department of Medical Oncology, Scientific Institute of Romagna for the Study and Treatment of Cancer, IRCCS, Meldola, Italy., Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah., Sarah Cannon Research Institute and Tennessee Oncology, Nashville, Tennessee., Department of Translational Medicine, QED Therapeutics Inc, San Francisco, California., Department of Biostatistics and Data Management, QED Therapeutics Inc, San Francisco, California., Department of Strategy and Operations, QED Therapeutics Inc, San Francisco, California., Department of Clinical Development, QED Therapeutics Inc, San Francisco, California., Institute of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California., Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.