• 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, and Tanios Bekaii-Saab.
• Milind Javle and Rachna T. Shroff, The University of Texas MD Anderson Cancer Center, Houston, TX; Maeve Lowery and Ghassan K. Abou-Alfa, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College, New York, NY; Karl Heinz Weiss and Christoph Springfeld, Universitäts Klinikum Heidelberg, Heidelberg, Germany; Mitesh J. Borad, Ramesh K. Ramanathan, and Tanios Bekaii-Saab, Mayo Clinic, Phoenix, AZ; Lipika Goyal and Andrew X. Zhu, Massachusetts General Hospital Cancer Center, Boston, MA; Saeed Sadeghi and Richard S. Finn, David Geffen School of Medicine at UCLA; Anthony El-Khoueiry, USC Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles; Robin Kate Kelley, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; Teresa Macarulla, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain; Ivan Borbath, Cliniques Universitaires Saint-Luc, Brussels; Eric Van Cutsem, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium; Su Pin Choo, National Cancer Centre of Singapore, Singapore; Do-Youn Oh, Seoul National University, Seoul, South Korea; Philip A. Philip, Karmanos Cancer Institute, Detroit, MI; Li-Tzong Chen, National Institute of Cancer Research and National Cheng Kung University Hospital, Tainan; Kun-Huei Yeh, National Taiwan University Hospital Cancer Center, and Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan; Thanyanan Reungwetwattana, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Kristen Ciombor, The Ohio State University Wexner Medical Center, Columbus, OH; and Anuradha Patel, Suman Sen, Dale Porter, and Randi Isaacs, Novartis Pharmaceuticals Corporation, East Hanover, NJ.
• J. Clin. Oncol. 2018 Jan 20; 36 (3): 276-282.

AbstractPurpose 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.

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