Milind JavleMaeve LoweryRachna T. ShroffKarl Heinz WeissChristoph SpringfeldMitesh J. BoradRamesh K. RamanathanLipika GoyalSaeed SadeghiTeresa MacarullaAnthony El-KhoueiryRobin Kate KelleyIvan BorbathSu Pin ChooDo Youn OhPhilip A. PhilipLi Tzong ChenThanyanan ReungwetwattanaEric Van CutsemKun Huei YehKristen CiomborRichard S. FinnAnuradha PatelSuman SenDale PorterRandi IsaacsAndrew X. ZhuGhassan K. Abou-AlfaTanios Bekaii-SaabNational Cheng Kung University HospitalBarbara Ann Karmanos Cancer InstituteNational Cancer Centre, SingaporeKU Leuven– University Hospital LeuvenUCSF Helen Diller Family Comprehensive Cancer CenterMayo Clinic Scottsdale-Phoenix, ArizonaNational Taiwan University College of MedicineFaculty of Medicine, Ramathibodi Hospital, Mahidol UniversityKeck School of Medicine of USCUniversity of Texas MD Anderson Cancer CenterSeoul National UniversityCliniques Universitaires Saint-Luc, BrusselsHospital Universitari Vall d'HebronMemorial Sloan-Kettering Cancer CenterDavid Geffen School of Medicine at UCLAOhio State UniversityUniversitätsklinikum HeidelbergMassachusetts General Hospital Cancer CenterNovartis Pharmaceuticals Corporation2019-08-232019-08-232018-01-20Journal of Clinical Oncology. Vol.36, No.3 (2018), 276-282152777550732183X2-s2.0-85040814328https://repository.li.mahidol.ac.th/handle/20.500.14594/45265© 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyMedicineArticleSCOPUS10.1200/JCO.2017.75.5009