TY - JOUR
T1 - Efficacy of BGJ398, a fibroblast growth factor receptor 1–3 inhibitor, in patients with previously treated advanced urothelial carcinoma with FGFR3 alterations
AU - Pal, Sumanta K.
AU - Rosenberg, Jonathan E.
AU - Hoffman-Censits, Jean H.
AU - Berger, Raanan
AU - Quinn, David I.
AU - Galsky, Matthew D.
AU - Wolf, Juergen
AU - Dittrich, Christian
AU - Keam, Bhumsuk
AU - Delord, Jean-Pierre
AU - Schellens, Jan H. M.
AU - Gravis, Gwenaelle
AU - Medioni, Jacques
AU - Maroto, Pablo
AU - Sriuranpong, Virote
AU - Charoentum, Chaiyut
AU - Burris, Howard A.
AU - Grünwald, Viktor
AU - Petrylak, Daniel
AU - Vaishampayan, Ulka
AU - Gez, Eliahu
AU - de Giorgi, Ugo
AU - Lee, Jae-Lyun
AU - Voortman, Jens
AU - Gupta, Sumati
AU - Sharma, Sunil
AU - Mortazavi, Amir
AU - Vaughn, David J.
AU - Isaacs, Randi
AU - Parker, Katie
AU - Chen, Xueying
AU - Yu, Kun
AU - Porter, Dale
AU - Porta, Diana Graus
AU - Bajorin, Dean F.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85049495380&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29848605
U2 - https://doi.org/10.1158/2159-8290.CD-18-0229
DO - https://doi.org/10.1158/2159-8290.CD-18-0229
M3 - Article
C2 - 29848605
SN - 2159-8274
VL - 8
SP - 812
EP - 821
JO - Cancer discovery
JF - Cancer discovery
IS - 7
ER -