Publication:
Phase II study of BGJ398 in patients with FGFR-Altered advanced cholangiocarcinoma

Issued Date

2018-01-20

Resource Type

Article

ISSN

15277755
0732183X

DOI

10.1200/JCO.2017.75.5009

Other identifier(s)

2-s2.0-85040814328

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Journal of Clinical Oncology. Vol.36, No.3 (2018), 276-282

Suggested Citation

Milind Javle, Maeve Lowery, Rachna T. Shroff, Karl Heinz Weiss, Christoph Springfeld, Mitesh J. Borad, Ramesh K. Ramanathan, Lipika Goyal, Saeed Sadeghi, Teresa Macarulla, Anthony El-Khoueiry, Robin Kate Kelley, Ivan Borbath, Su Pin Choo, Do Youn Oh, Philip A. Philip, Li Tzong Chen, Thanyanan Reungwetwattana, Eric Van Cutsem, Kun Huei Yeh, Kristen Ciombor, Richard S. Finn, Anuradha Patel, Suman Sen, Dale Porter, Randi Isaacs, Andrew X. Zhu, Ghassan K. Abou-Alfa, Tanios Bekaii-Saab Phase II study of BGJ398 in patients with FGFR-Altered advanced cholangiocarcinoma. Journal of Clinical Oncology. Vol.36, No.3 (2018), 276-282. doi:10.1200/JCO.2017.75.5009 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/45265

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Title

Phase II study of BGJ398 in patients with FGFR-Altered advanced cholangiocarcinoma

Author(s)

Milind Javle
 Maeve Lowery
 Rachna T. Shroff
 Karl Heinz Weiss
 Christoph Springfeld
 Mitesh J. Borad
 Ramesh K. Ramanathan
 Lipika Goyal
 Saeed Sadeghi
 Teresa Macarulla
 Anthony El-Khoueiry
 Robin Kate Kelley
 Ivan Borbath
 Su Pin Choo
 Do Youn Oh
 Philip A. Philip
 Li Tzong Chen
 Thanyanan Reungwetwattana
 Eric Van Cutsem
 Kun Huei Yeh
 Kristen Ciombor
 Richard S. Finn
 Anuradha Patel
 Suman Sen
 Dale Porter
 Randi Isaacs
 Andrew X. Zhu
 Ghassan K. Abou-Alfa
 Tanios Bekaii-Saab

Other Contributor(s)

National Cheng Kung University Hospital
 Barbara Ann Karmanos Cancer Institute
 National Cancer Centre, Singapore
 KU Leuven– University Hospital Leuven
 UCSF Helen Diller Family Comprehensive Cancer Center
 Mayo Clinic Scottsdale-Phoenix, Arizona
 National Taiwan University College of Medicine
 Faculty of Medicine, Ramathibodi Hospital, Mahidol University
 Keck School of Medicine of USC
 University of Texas MD Anderson Cancer Center
 Seoul National University
 Cliniques Universitaires Saint-Luc, Brussels
 Hospital Universitari Vall d'Hebron
 Memorial Sloan-Kettering Cancer Center
 David Geffen School of Medicine at UCLA
 Ohio State University
 Universitätsklinikum Heidelberg
 Massachusetts General Hospital Cancer Center
 Novartis Pharmaceuticals Corporation

Abstract

© 2017 by American Society of Clinical Oncology. Purpose No standard treatment exists for patients with cholangiocarcinoma for whom first-line gemcitabine-based therapy fails. Fibroblast growth factor receptor 2 (FGFR2) fusions/translocations are present in 13% to 17% of intrahepatic cholangiocarcinomas. BGJ398, an orally bioavailable, selective pan-FGFR kinase inhibitor, has shown preliminary clinical activity against tumors with FGFR alterations. Methods A multicenter, open-label, phase II study (ClinicalTrials.gov identifier: NCT02150967) evaluated BGJ398 antitumor activity in patients age $ 18 years with advanced or metastatic cholangiocarcinoma containing FGFR2 fusions or other FGFR alterations whose disease had progressed while receiving prior therapy. Patients received BGJ398 125 mg once daily for 21 days, then 7 days off (28-day cycles). The primary end point was investigator-assessed overall response rate. Results Sixty-one patients (35 women; median age, 57 years) with FGFR2 fusion (n = 48), mutation (n = 8), or amplification (n = 3) participated. At the prespecified data cutoff (June 30, 2016), 50 patients had discontinued treatment. All responsive tumors contained FGFR2 fusions. The overall response rate was 14.8% (18.8% FGFR2 fusions only), disease control rate was 75.4% (83.3% FGFR2 fusions only), and estimated median progression-free survival was 5.8 months (95% CI, 4.3 to 7.6 months). Adverse events included hyperphosphatemia (72.1% all grade), fatigue (36.1%), stomatitis (29.5%), and alopecia (26.2%). Grade 3 or 4 treatment-related adverse events occurred in 25 patients (41%) and included hyperphosphatemia (16.4%), stomatitis (6.6%), and palmar-plantar erythrodysesthesia (4.9%). Conclusion BGJ398 is a first-in-class FGFR kinase inhibitor with manageable toxicities that shows meaningful clinical activity against chemotherapy-refractory cholangiocarcinoma containing FGFR2 fusions. This promising antitumor activity supports continued development of BGJ398 in this highly selected patient population.

Keyword(s)

Biochemistry, Genetics and Molecular Biology
 Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/45265

Collections

Scopus 2018