FGFR Kinase Inhibitor in FGFR-Altered Advanced Cholangiocarcinoma


Key Points

  • Disease control rates with BGJ398 were 75.4% among all patients with advanced cholangiocarcinoma and 83.3% in those with FGFR2 fusions.
  • Grade 3 or 4 treatment-related adverse events occurred in 41% of patients.

In a phase II trial reported in the Journal of Clinical Oncology, Javle et al found that the oral pan-fibroblast growth factor receptor (FGFR) kinase inhibitor BGJ398 was active in FGFR-altered advanced cholangiocarcinoma. It is estimated that FGFR2 fusions/translocations are present in 13% to 17% of cases of intrahepatic cholangiocarcinoma.

Study Details

In the study, 61 patients (57% women; median age = 57 years) with disease progression on prior therapy received BGJ398 at 125 mg once daily for 21 days with 7 days off. Among the 61 patients, 48 had FGFR2 fusion, 8 had a mutation, and 3 had amplification. The primary endpoint was investigator-assessed overall response rate.

Response Rate

The overall response rate was 14.8%. All responses occurred in patients with FGFR2 fusions (response rate = 18.8%). The disease control rate was 75.4% among all patients and 83.3% in those with FGFR2 fusions. Median progression-free survival was 5.8 months.

Adverse Events

Common adverse events of any grade included hyperphosphatemia (72%), fatigue (36%), stomatitis (30%), and alopecia (26%). Grade 3 or 4 treatment-related adverse events occurred in 41%, including hyperphosphatemia in 16%, stomatitis in 7%, and palmar-plantar erythrodysesthesia in 5%.

The investigators concluded: “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.”

The study was supported by Novartis Pharmaceuticals.

Milind Javle, MD, of the Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.