Background: Treatments are sparse for patients with advanced cholangiocarcinoma after progression on first-line gemcitabine-based therapy. FGFR2 fusions or rearrangements exist in 10-16% of patients with intrahepatic cholangiocarcinoma. Infigratinib is really a selective, ATP-competitive inhibitor of fibroblast growth factor receptors. We aimed to judge the antitumour activity of infigratinib in patients with in your area advanced or metastatic cholangiocarcinoma, FGFR2 alterations, and former gemcitabine-based treatment.
Methods: This multicentre, open-label, single-arm, phase 2 study employed patients from 18 academic centres and hospitals in the united states, Belgium, The country, Germany, Singapore, Taiwan, and Thailand. Qualified participants were aged 18 years or older, had histologically or cytologically confirmed, in your area advanced or metastatic cholangiocarcinoma and FGFR2 fusions or rearrangements, and were formerly given a minumum of one gemcitabine-that contains regimen. Patients received 125 mg of dental infigratinib once daily for a 3 week period of 28-day cycles until disease progression, intolerance, withdrawal of consent, or dying. Radiological tumor evaluation ended at baseline and each 8 days until disease progression via CT or MRI from the chest, abdomen, and pelvis. The main endpoint was objective response rate, understood to be the proportion of patients having a best overall response of the confirmed complete or partial response, as assessed by blinded independent central review (BICR) based on Response Evaluation Criteria in Solid Tumors, version 1.1. The main outcome and safety were analysed within the full analysis set, which comprised all patients who received a minumum of one dose of infigratinib. This trial is registered with ClinicalTrials.gov, NCT02150967, and it is ongoing.
Findings: Between June 23, 2014, and March 31, 2020, 122 patients were enrolled into our study, who 108 with FGFR2 fusions or rearrangements received a minumum of one dose of infigratinib and comprised the entire analysis set. Following a median follow-from 10·6 several weeks (IQR 6·2-15·6), the BICR-assessed objective response rate was 23·1% (95% CI 15·6-32·2 25 of 108 patients), with one confirmed complete response inside a patient who only had non-target lesions identified at baseline and 24 partial responses. The most typical treatment-emergent adverse occasions associated with a grade were hyperphosphataemia (n=83), stomatitis (n=59), fatigue (n=43), and alopecia (n=41). The most typical ocular toxicity was dry eyes (n=37). Central serous retinopathy-like and retinal pigment epithelial detachment-like occasions happened in 18 (17%) patients, which ten (9%) were grade 1, seven (6%) were grade 2, and something (1%) was grade 3. There have been no treatment-related deaths.
Interpretation: Infigratinib has promising clinical activity along with a manageable adverse event profile in formerly treated patients with in your area advanced or metastatic cholangiocarcinoma harbouring FGFR2 gene fusions or rearrangements, and thus represents a possible new therapeutic option within this setting.