Phase II study of BGJ398 in patients with FGFR-Altered advanced cholangiocarcinoma
Journal
Journal of Clinical Oncology
Journal Volume
36
Journal Issue
3
Pages
276-282
Date Issued
2018
Author(s)
Javle M.
Lowery M.
Shroff R.T.
Weiss K.H.
Springfeld C.
Borad M.J.
Ramanathan R.K.
Goyal L.
Sadeghi S.
Macarulla T.
El-Khoueiry A.
Kelley R.K.
Borbath I.
Choo S.P.
Oh D.-Y.
Philip P.A.
Chen L.-T.
Reungwetwattana T.
Van Cutsem E.
Ciombor K.
Finn R.S.
Patel A.
Sen S.
Porter D.
Isaacs R.
Zhu A.X.
Abou-Alfa G.K.
Bekaii-Saab T.
Abstract
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. ? 2017 by American Society of Clinical Oncology.
SDGs
Other Subjects
alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; creatinine; fibroblast growth factor receptor; hemoglobin; infigratinib; magnesium; triacylglycerol lipase; 3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-(6-(4-(4-ethylpiperazin-1-yl)-phenylamino)pyrimidin-4-yl)-1-methylurea; antineoplastic agent; carbanilamide derivative; FGFR2 protein, human; fibroblast growth factor receptor 2; protein kinase inhibitor; pyrimidine derivative; tumor marker; abdominal pain; adult; advanced cancer; adverse event; aged; alopecia; anemia; antineoplastic activity; arthralgia; Article; bile duct carcinoma; blurred vision; body weight loss; cancer control; cancer growth; cancer patient; cellulitis; cholangitis; constipation; decreased appetite; dehydration; diarrhea; drug dose reduction; drug efficacy; drug withdrawal; dry eye; dry skin; dysgeusia; dyspepsia; eye toxicity; fatigue; female; FGFR gene; FGFR1 gene; FGFR2 gene; FGFR3 gene; fusion gene; gene amplification; gene mutation; hand foot syndrome; headache; human; hypercalcemia; hyperphosphatemia; hypertransaminasemia; hyponatremia; hypophosphatemia; liver failure; maculopapular rash; major clinical study; male; mucosal dryness; multicenter study; multiple cycle treatment; myalgia; nail disease; nausea; onycholysis; onychomadesis; open study; pain; paronychia; phase 2 clinical trial; priority journal; progression free survival; rash; receptor gene; sepsis; side effect; stomatitis; traumatic hematoma; treatment response; vomiting; xerostomia; antagonists and inhibitors; bile duct cancer; bile duct carcinoma; clinical trial; disease exacerbation; drug administration; gene fusion; genetic predisposition; genetics; middle aged; mortality; mutation; oral drug administration; pathology; phenotype; prospective study; secondary; time factor; Administration, Oral; Adult; Aged; Antineoplastic Agents; Bile Duct Neoplasms; Biomarkers, Tumor; Cholangiocarcinoma; Disease Progression; Drug Administration Schedule; Gene Amplification; Gene Fusion; Genetic Predisposition to Disease; Humans; Middle Aged; Mutation; Phenotype; Phenylurea Compounds; Progression-Free Survival; Prospective Studies; Protein Kinase Inhibitors; Pyrimidines; Receptor, Fibroblast Growth Factor, Type 2; Time Factors
Publisher
American Society of Clinical Oncology
Type
journal article