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A pilot study of Pan-FGFR inhibitor ponatinib in patients with FGFR-altered advanced cholangiocarcinoma
Ist Teil von
Investigational new drugs, 2022-02, Vol.40 (1), p.134-141
Ort / Verlag
New York: Springer US
Erscheinungsjahr
2022
Quelle
MEDLINE
Beschreibungen/Notizen
Summary
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.