Efficacy of BGJ398, a Fibroblast Growth Factor Receptor 1–3 Inhibitor, in Patients with Previously Treated Advanced Urothelial Carcinoma with<i>FGFR3</i>Alterations

  • Sumanta K. Pal
    1City of Hope, Duarte, California.
  • Jonathan E. Rosenberg
    2Memorial Sloan Kettering Cancer Center, New York, New York.
  • Jean H. Hoffman-Censits
    3Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Raanan Berger
    4The Chaim Sheba Medical Center, Ramat Gan, Israel.
  • David I. Quinn
    5USC Norris Cancer Center, Los Angeles, California.
  • Matthew D. Galsky
    6The Mount Sinai Hospital, New York, New York.
  • Juergen Wolf
    7Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany.
  • Christian Dittrich
    8Applied Cancer Research-Institution for Translational Research Vienna (ACR-ITR VIEnna), Kaiser-Franz-Josef-Spital, Vienna, Austria.
  • Bhumsuk Keam
    9Seoul National University Hospital, Seoul, South Korea.
  • Jean-Pierre Delord
    10IUCT Oncopole, Toulouse, France.
  • Jan H.M. Schellens
    11The Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Gwenaelle Gravis
    12Institut Paoli Calmettes, Marseilles, France.
  • Jacques Medioni
    13Hôpital Européen Georges Pompidou, Paris, France.
  • Pablo Maroto
    14Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
  • Virote Sriuranpong
    15Faculty of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
  • Chaiyut Charoentum
    16Maharaj Nakorn Chiangmai Hospital, Chiang Mai, Thailand.
  • Howard A. Burris
    17Sarah Cannon Research Institute, Nashville, Tennessee.
  • Viktor Grünwald
    18Medical School Hannover, Clinic for Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover, Germany.
  • Daniel Petrylak
    19Yale School of Medicine, New Haven, Connecticut.
  • Ulka Vaishampayan
    20Wayne State University/Karmanos Cancer Institute, Detroit, Michigan.
  • Eliahu Gez
    21Tel-Aviv Sourasky Medical Center (Ichilov), Tel Aviv, Israel.
  • Ugo De Giorgi
    22Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
  • Jae-Lyun Lee
    23Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • Jens Voortman
    24VU University Medical Center, Cancer Center Amsterdam, Amsterdam, the Netherlands.
  • Sumati Gupta
    25Huntsman Cancer Institute (University of Utah), Salt Lake City, Utah.
  • Sunil Sharma
    25Huntsman Cancer Institute (University of Utah), Salt Lake City, Utah.
  • Amir Mortazavi
    26The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
  • David J. Vaughn
    27Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania.
  • Randi Isaacs
    28Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
  • Katie Parker
    28Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
  • Xueying Chen
    28Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
  • Kun Yu
    29Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
  • Dale Porter
    29Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
  • Diana Graus Porta
    30Novartis Pharma AG, Basel, Switzerland.
  • Dean F. Bajorin
    2Memorial Sloan Kettering Cancer Center, New York, New York.

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<jats:title>Abstract</jats:title><jats:p>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.</jats:p><jats:p>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. Cancer Discov; 8(7); 812–21. ©2018 AACR.</jats:p><jats:p>This article is highlighted in the In This Issue feature, p. 781</jats:p>

収録刊行物

  • Cancer Discovery

    Cancer Discovery 8 (7), 812-821, 2018-07-01

    American Association for Cancer Research (AACR)

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