A pilot study of Pan-FGFR inhibitor ponatinib in patients with FGFR-altered advanced cholangiocarcinoma

帕纳替尼 医学 内科学 成纤维细胞生长因子受体 肿瘤科 成纤维细胞生长因子受体1 耐火材料(行星科学) 酪氨酸激酶抑制剂 癌症研究 成纤维细胞生长因子 血管生成 药理学 酪氨酸激酶 癌症 生物 尼罗替尼 受体 天体生物学
作者
Daniel H. Ahn,Fernando C. Maluf,Peter Masci,Heidi E. Kosiorek,Thorvardur R. Halfdanarson,Kabir Mody,Hani M. Babiker,Thomas DeLeon,Mohamad Bassam Sonbol,Gregory J. Gores,Rory L. Smoot,Tanios Bekaii-Saab,Amit Mahipal,Aaron S. Mansfield,Nguyen H Tran,Joleen M. Hubbard,Mitesh J. Borad
出处
期刊:Investigational New Drugs [Springer Science+Business Media]
卷期号:40 (1): 134-141 被引量:11
标识
DOI:10.1007/s10637-021-01170-x
摘要

Background Biliary tract cancers (BTC) are rare, chemo resistant and are associated with a poor prognosis. Preclinical and early clinical work had demonstrated interesting anti-tumor activity from targeting fibroblast growth factor receptor (FGFR) pathway. We hypothesized that ponatinib, a multi-targeted tyrosine kinase inhibitor with activity against FGFR, would be active in BTC patients with FGFR alterations. Methods This was a multi-center, single institution pilot study of ponatinib in patients with advanced, refractory BTC with FGFR alterations. The primary end point was overall response rate, with secondary points of overall survival (OS), progression-free survival (PFS) and Health Related Quality of Life (HRQoL) assessment. Results Twelve patients were enrolled prior to early termination of the trial. Partial responses were observed in 1 from 12 patients. Median PFS was 2.4 months and median OS was 15.7 months. All observed toxicities were manageable and reversible. Toxicities were mild, with lymphopenia (75%), rash (63%) and fatigue (50%) being the most frequent. No significant detriment in global QoL was observed. Conclusions Ponatinib as a single agent in FGFR altered BTC is tolerable with limited clinical activity. This is the first report of prospective assessment of FGFR inhibition in BTC using ponatinib, and the first study to report its effect on HRQoL. Further development of ponatinib will involve correlative studies to better refine patient selection, focus on combinations with other molecular targeted agents, conventional cytotoxic chemotherapy, and studies to better understand mechanisms of treatment resistance.
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