Efficacy of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Inhibitor, in Patients with Previously Treated Advanced Urothelial Carcinoma with FGFR3 Alterations

被引：208

作者：

Pal, Sumanta K. ^{[1
]}

Rosenberg, Jonathan E. ^{[2
]}

Hoffman-Censits, Jean H. ^{[3
]}

Berger, Raanan ^{[4
]}

Quinn, David I. ^{[5
]}

Galsky, Matthew D. ^{[6
]}

Wolf, Juergen ^{[7
]}

Dittrich, Christian ^{[8
]}

Keam, Bhumsuk ^{[9
]}

Delord, Jean-Pierre ^{[10
]}

Schellens, Jan H. M. ^{[11
]}

Gravis, Gwenaelle ^{[12
]}

Medioni, Jacques ^{[13
]}

Maroto, Pablo ^{[14
]}

Sriuranpong, Virote ^{[15
,16
]}

Charoentum, Chaiyut ^{[17
]}

Burris, Howard A. ^{[18
]}

Grunwald, Viktor ^{[19
]}

Petrylak, Daniel ^{[20
]}

Vaishampayan, Ulka ^{[21
]}

Gez, Eliahu ^{[22
]}

De Giorgi, Ugo ^{[23
]}

Lee, Jae-Lyun ^{[24
]}

Voortman, Jens ^{[25
]}

Gupta, Sumati ^{[26
]}

Sharma, Sunil ^{[26
]}

Mortazavi, Amir ^{[27
]}

Vaughn, David J. ^{[28
]}

Isaacs, Randi ^{[29
]}

Parker, Katie ^{[29
]}

Chen, Xueying ^{[29
]}

Yu, Kun ^{[30
]}

Porter, Dale ^{[30
]}

Porta, Diana Graus ^{[31
]}

Bajorin, Dean F. ^{[2
]}

机构：

[1] City Hope Natl Med Ctr, Duarte, CA USA

[2] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA

[3] Thomas Jefferson Univ, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA

[4] Chaim Sheba Med Ctr, Ramat Gan, Israel

[5] USC Norris Canc Ctr, Los Angeles, CA USA

[6] Mt Sinai Hosp, New York, NY 10029 USA

[7] Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany

[8] Kaiser Franz Josef Spital, ACR ITR VIEnna, Appl Canc Res Inst Translat Res Vienna, Vienna, Austria

[9] Seoul Natl Univ Hosp, Seoul, South Korea

[10] IUCT Oncopole, Toulouse, France

[11] Netherlands Canc Inst, Amsterdam, Netherlands

[12] Inst Paoli Calmettes, Marseilles, France

[13] Hop Europeen Georges Pompidou, Paris, France

[14] Hosp Santa Creu & Sant Pau, Barcelona, Spain

[15] Chulalongkorn Univ, Fac Med, Bangkok, Thailand

[16] King Chulalongkorn Mem Hosp, Bangkok, Thailand

[17] Maharaj Nakorn Chiangmai Hosp, Chiang Mai, Thailand

[18] Sarah Cannon Res Inst, Nashville, TN USA

[19] Clin Hematol Hemostasis Oncol & Stem Cell Transp, Med Sch Hannover, Hannover, Germany

[20] Yale Sch Med, New Haven, CT USA

[21] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA

[22] Tel Aviv Sourasky Med Ctr Ichilov, Tel Aviv, Israel

[23] Inst Sci Romagnolo Studio & Cura Tumori IRST IRC, Meldola, Italy

[24] Univ Ulsan, Asan Med Ctr, Coll Med, Seoul, South Korea

[25] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Amsterdam, Netherlands

[26] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA

[27] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA

[28] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[29] Novartis Pharmaceut, E Hanover, NJ USA

[30] Novartis Inst BioMed Res, Cambridge, MA USA

[31] Novartis Pharma AG, Basel, Switzerland

来源：

CANCER DISCOVERY | 2018年 / 8卷 / 07期

关键词：

CISPLATIN-INELIGIBLE PATIENTS; ACQUIRED-RESISTANCE; GENETIC ALTERATIONS; BLADDER-CANCER; SINGLE-ARM; MULTICENTER; PEMBROLIZUMAB; NVP-BGJ398; MUTATIONS;

D O I：

10.1158/2159-8290.CD-18-0229

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 87 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. (C) 2018 AACR.

引用

页码：812 / 821

页数：10

共 32 条

[31] A Functional Genetic Screen Identifies the Phosphoinositide 3-kinase Pathway as a Determinant of Resistance to Fibroblast Growth Factor Receptor Inhibitors in FGFR Mutant Urothelial Cell Carcinoma [J].