@article{9589187e0599487a9e9cc630bf4e468a,
title = "Efficacy of BGJ398, a fibroblast growth factor receptor 1–3 inhibitor, in patients with previously treated advanced urothelial carcinoma with FGFR3 alterations",
abstract = "BGJ398, a potent and selective pan-FGFR antagonist, was prospectively evaluated in patients with metastatic urothelial carcinoma bearing a diverse array of FGFR3 alterations. Patients (N = 67) who were unable to receive platinum chemotherapy were enrolled. The majority (70.1%) had received two or more prior antineoplastic therapies. BGJ398 was administered orally at 125 mg/day on a 3 weeks on, 1 week off schedule until unacceptable toxicity or progression. The primary endpoint was the response rate. Among 67 patients treated, an overall response rate of 25.4% was observed and an additional 38.8% of patients had disease stabilization, translating to a disease control rate of 64.2%. The most common treatment-emergent toxicities were hyperphosphatemia, elevated creatinine, fatigue, constipation, and decreased appetite. Further examination of BGJ398 in this disease setting is warranted. SIGnIFICAnCE: BJG398 is active in patients with alterations in FGFR3, resulting in both reductions in tumor volume and stabilization of disease. Our data highlight putative mechanisms of resistance to the agent, which may be useful in following disease status.",
author = "Pal, {Sumanta K.} and Rosenberg, {Jonathan E.} and Hoffman-Censits, {Jean H.} and Raanan Berger and Quinn, {David I.} and Galsky, {Matthew D.} and Juergen Wolf and Christian Dittrich and Bhumsuk Keam and Delord, {Jean Pierre} and Schellens, {Jan H.M.} and Gwenaelle Gravis and Jacques Medioni and Pablo Maroto and Virote Sriuranpong and Chaiyut Charoentum and Burris, {Howard A.} and Viktor Gr{\"u}nwald and Daniel Petrylak and Ulka Vaishampayan and Eliahu Gez and {De Giorgi}, Ugo and Lee, {Jae Lyun} and Jens Voortman and Sumati Gupta and Sunil Sharma and Amir Mortazavi and Vaughn, {David J.} and Randi Isaacs and Katie Parker and Xueying Chen and Kun Yu and Dale Porter and Porta, {Diana Graus} and Bajorin, {Dean F.}",
note = "Funding Information: S.K. Pal has received honoraria from the speakers bureau of Genentech and is a consultant/advisory board member for Pfizer, Ipsen, Exelixis, Eisai, BMS, Astellas, and Novartis. J.E. Rosenberg reports receiving commercial research grants from Novartis, Roche/ Genentech, Astellas, Seattle Genetics, and Bayer; has received honoraria from the speakers bureaus of Chugai and AstraZeneca; has ownership interest (including patents) in Illumina; and is a consultant/advisory board member for Bioclin, AstraZeneca, and Bayer. J.H. Hoffman-Censits reports receiving commercial research support from Genentech and is a consultant/advisory board member for Foundation Medicine. D.I. Quinn is a consultant/advisory board member for Novartis, Janssen, Bayer Healthcare, Genentech, BMS, Merck, AstraZeneca, Pfizer, and Astellas. M.D. Galsky is a consultant/advisory board member for Merck, Genentech, AstraZeneca, and BMS. J. Wolf has received honoraria from the speakers bureau of Novartis and is a consultant/advisory board member for the same. C. Dittrich has received honoraria from the speakers bureau of Novartis. V. Sriuranpong has received honoraria from the speakers bureaus of AstraZeneca, Novartis, Roche, Pfizer, Sanofi, Merck Sorono, Eisai, Beringer, Taiho, Janssen, and MSD; served as an advisory board member for MSD, Novartis, Pfizer, Roche, and Eisai; and has received clinical research support through institution from AstraZeneca, Novartis, Roche, Pfizer, Sanofi, Boehringer, Eisai, Taiho, Lilly, BMS, and MSD. V. Gr{\"u}nwald reports receiving commercial research grants from Novartis, BMS, AstraZeneca, MSD, and Pfizer; has received honoraria from the speakers bureaus of BMS, Novartis, MSD, Roche, Pfizer, Ipsen, AstraZeneca, EISAI, EUSAPharma, and MedKomAkademi; and is a consultant/advisory board member for BMS, Novartis, MSD, Pfizer, Roche, and EUSAPharma. D. Petry-lak reports receiving commercial research grants from Genentech, Merck, Lilly, Novartis, Bayer, Astellas, and Pfizer; has received honoraria from the speakers bureaus of Genentech, Bayer, Merck, Astellas, Lilly, Pfizer, and Bristol; has ownership interest (including patents) in Tyme and Bellicum; and has received remuneration from Sanofi and Celgene. S. Gupta reports receiving commercial research grants from Parexel International, Five Prime Therapeutics, LSK, Methylgene, Inc., University of Minnesota, Hoosier Oncology Group, Viralytics, Rexahn, Incyte, Novartis, Bristol-Myers Squibb, Merck, and Clovis, and has ownership interest (including patents) in Salarius Pharmaceutical. A. Mortazavi is a consultant/advisory board member for Genentech-Roche and has received remuneration from Motive Medical Intelligence. K. Parker has received remuneration from Novartis. D.F. Bajorin has received honoraria from the speakers bureau of Merck and is a consultant/advisory board member for Merck, Pfizer, Bristol-Myers Squibb, Urogen, Genentech, and Eli Lilly. No potential conflicts of interest were disclosed by the other authors. Funding Information: Neelesh Sharma (Novartis Pharmaceuticals), Daniel Carreon (Novartis Pharmaceuticals), Markus Riester (Novartis Pharmaceuticals), Kun Xu (Novartis Pharmaceuticals), and Sapna Chhagan (Novartis Pharmaceuticals) are thanked for their contributions to the study and manuscript. Funding for this study was provided by Novartis. D.F. Bajorin and J.E. Rosenberg acknowledge a core grant for the Memorial Sloan Kettering Cancer Center (P30 CA008748).",
year = "2018",
month = jul,
doi = "10.1158/2159-8290.CD-18-0229",
language = "English (US)",
volume = "8",
pages = "812--821",
journal = "Cancer Discovery",
issn = "2159-8274",
publisher = "American Association for Cancer Research Inc.",
number = "7",
}