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

被引：202

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 50 条

[21] Blockade of the fibroblast growth factor receptor (FGFR) system by the novel FGFR inhibitor BGJ398 modulates oncogenic signaling in human gastric cancer cells, endothelial cells and pericytes
Moser, Christian
Hackl, Christina
Schlitt, Hans J.
Geissler, Edward K.
Lang, Sven A.
CANCER RESEARCH, 2012, 72
[22] Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study (vol 35, pg 157, 2017)
Nogova
JOURNAL OF CLINICAL ONCOLOGY, 2017, 35 (08) : 926 - 926
[23] Unique Morphologic Characteristics of High Grade Urothelial Carcinoma with Fibroblast Growth Factor Receptor-3 (FGFR3) Gene Mutations
Al-Ahmadie, H. A.
Lin, O.
Iyer, G. V.
Heguy, A.
Fine, S. W.
Tickoo, S. K.
Hanrahan, A. J.
Bajorin, D. F.
Reuter, V. E.
Solit, D. B.
Milowsky, M. I.
LABORATORY INVESTIGATION, 2010, 90 : 174A - 174A
[24] Unique Morphologic Characteristics of High Grade Urothelial Carcinoma with Fibroblast Growth Factor Receptor-3 (FGFR3) Gene Mutations
Al-Ahmadie, H. A.
Liu, O.
tyer, G. V.
Heguy, A.
Gopalan, A.
Fine, S. W.
Tiekoo, S. K.
Hanrahan, A. J.
Bajorin, D. F.
Reuter, V. E.
Solit, D. B.
Milowsky, M. I.
MODERN PATHOLOGY, 2010, 23 : 174A - 174A
[25] Fibroblast growth factor receptor 3 (FGFR3) expression in malignant lymphomas
Larson, Andrew
Cook, James R.
APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY, 2008, 16 (04) : 322 - 325
[26] Expression of Fibroblast Growth Factor Receptor 3 ( FGFR3) & Vascular Endothelial Growth Factor (VEGF) in malignant tumours of the urothelial tract
Arora, A.
Nalwa, A.
Rao, M.
Elhence, P.
Choudhary, G. R.
VIRCHOWS ARCHIV, 2024, 485 : S520 - S520
[27] Fibroblast kinase 1-3 inhibitor BGJ398 in patients with FGFR1 amplified squamous non-small cell lung cancer treated in a phase I study: evaluation of tumor tissue and response at a single center
Nogova, L.
Malchers, F.
Bitter, E.
Michels, S.
Fischer, R.
Scheffler, M.
Gardizi, M.
Brandes, V.
Scheel, A. H.
Kambartel, K.
Krueger, S.
Serke, M.
Isaacs, R.
Porter, D.
Buettner, R.
Thomas, R. K.
Wolf, J.
ONCOLOGY RESEARCH AND TREATMENT, 2017, 40 : 137 - +
[28] Vofatamab Fibroblast growth factor receptor 3 (FGFR-3) antibody Treatment of urothelial carcinoma
Hanna, K. S.
DRUGS OF THE FUTURE, 2020, 45 (06) : 383 - 388
[29] Urothelial carcinoma of the bladder in patients aged 30 years or younger: clinicopathological analysis and expression of fibroblast growth factor receptor 3 (FGFR3) of 45 cases
Haichao Huang
Mengkui Sun
Xin Li
Jie Jin
Medical Oncology, 2015, 32
[30] Urothelial carcinoma of the bladder in patients aged 30 years or younger: clinicopathological analysis and expression of fibroblast growth factor receptor 3 (FGFR3) of 45 cases
Huang, Haichao
Sun, Mengkui
Li, Xin
Jin, Jie
MEDICAL ONCOLOGY, 2015, 32 (05)

← 1 2 3 4 5 →