Cholangiocarcinoma (CCA)

Truseltiq™ (infigratinib), a kinase inhibitor, is indicated for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as determined by a test approved by the US Food and Drug Administration (FDA).1 

Cholangiocarcinomas (CCAs) are cancers that develop in the bile ducts extending from the liver and gallbladder to the small intestine. The FGFR2 gene encodes FGFR2 proteins, which are thought to be involved in cell proliferation, differentiation, and angiogenesis. Genetic abnormalities in FGFR2 are identified in 15% to 20% of patients with CCA, who have a median 5-year survival rate of 9%. In the United States and the European Union, CCA is identified in about 20,000 persons annually.2-4 

Infigratinib received accelerated approval from the FDA on May 28, 2021.5 The drug is available as 25- and 100-mg capsules. Both the capsules are available in hard gelatine form with a white opaque body. The recommended dose is 125 mg taken orally once daily for 21 consecutive days in a 28-day cycle; dosing is continued until disease progression or unacceptable toxicity. Dosage modifications are required for patients with hepatic or renal impairment. The drug is taken on an empty stomach with a minimum interval of 1 hour before or 2 hours after food intake, at approximately the same time each day. The capsules are swallowed whole with water.1,2 

The FDA also approved Foundation Medicine’s FoundationOne®CDx comprehensive genomic profiling test to select patients with an FGFR2 fusion or another rearrangement as a registrational companion diagnostic device for treatment with infigratinib. For the treatment of CCA, infigratinib received Orphan Drug and Fast Track designations.4,5

Get full prescribing information for Truseltiq at MPR

Infigratinib is an orally bioavailable pan inhibitor of human fibroblast growth factor receptors (FGFRs) with potential antiangiogenic and antineoplastic activities. Credit: PubChem

Mechanism of Action

Truseltiq (infigratinib) is a small-molecule, ATP-competitive tyrosine kinase inhibitor of FGFR with half-maximal inhibitory concentration (IC50) values of 1.1, 1, 2, and 61 nM for FGFR1, FGFR2, FGFR3, and FGFR4, respectively. FGFR abnormalities in tumors can result in constitutive FGFR signaling, which promotes the growth and survival of cancerous cells. By specifically binding to and inhibiting the activities of FGFR, Truseltiq prevents downstream signaling cascades. By reducing cancer cell proliferation, it causes tumor cell death.4,6

Efficacy in Trials and Trial Results

FDA approval of infigratinib for the treatment of cholangiocarcinoma was based on the results of a multicenter, open-label, single-arm phase 2 clinical trial (NCT02150967). To assess the effectiveness of Truseltiq, the trial enrolled 108 patients with previously treated, unresectable, locally advanced or metastatic CCA with an FGFR2 fusion or rearrangement. Participants received infigratinib at a dose of 125 mg once daily for 21 consecutive days, followed by a 7-day interval, in a 28-day cycle until disease progression or unacceptable toxicity. The study measures were the overall response rate (ORR) and duration of response (DOR) as evaluated by blinded independent central review according to version 1.1 of the Response Evaluation Criteria in Solid Tumors (RECIST). The ORR was 23%, with 1% of patients achieving complete response and 22% a partial response.The median DOR was 5 months.2,4 

Warnings, Precautions, and Adverse Reactions

The most common (incidence ≥20%) adverse reactions in the clinical study of patients with CCA treated with Truseltiq were nail toxicity, stomatitis, dry eye, fatigue, alopecia, palmar-plantar erythrodysesthesia syndrome, arthralgia, dysgeusia, constipation, abdominal pain, dry mouth, eyelash changes, diarrhea, dry skin, decreased appetite, blurry vision, and vomiting. Laboratory abnormalities observed in the Truseltiq-treated patients (incidence ≥20%) included increased creatinine and phosphate; reduced phosphate; increased alkaline phosphatase; reduced hemoglobin; increased alanine aminotransferase, lipase, and calcium; decreased number of lymphocytes; decreased sodium; increased triglycerides, aspartate aminotransferase, and urate; decreased platelets, leukocytes, and albumin; increased bilirubin; and reduced potassium. 1,2,4,7 

Ocular toxicity due to Truseltiq can result in retinal pigment epithelial detachment. Patients should undergo a comprehensive ophthalmologic examination, including optical coherence tomography, before starting Truseltiq, again at 1 and 3 months, and then every 3 months thereafter during treatment. The drug is withheld if required. Optical coherence tomography (OCT) is also recommended for patients with asymptomatic retinal pigment epithelial detachment (RPED). The median time to first onset of RPED is 26 days.1  

Laboratory abnormalities such as hyperphosphatemia can result in soft tissue mineralization, cutaneous calcinosis, non-uremic calciphylaxis, vascular calcification, and myocardial calcification. The drug must be withheld, the dosage reduced, or the drug permanently discontinued as recommended in such cases.1  

Infigratinib can cause embryo-fetal toxicity if administered to pregnant women. Patients with reproductive potential must be informed of the risk of the drug to the fetus and advised to practice contraception during treatment with TRUSELTIQ and for one month after the final dose. It is important for female patients to inform their healthcare provider whether they are pregnant or plan to become pregnant before starting treatment with Truseltiq.1,7 


  1. TRUSELTIQ (infigratinib) capsules, for oral use. Highlights of prescribing information. QED Therapeutics; 2021. Revised may 2021. Accessed August 8, 2022.
  2. Kang C. Infigratinib: first approval [published correction appears in Drugs. 2022;82(1):93]. Drugs. 2021;81(11):1355-1360. doi:10.1007/s40265-021-01567-1
  3. Fala L. Truseltiq (Infigratinib) new targeted therapy fda approved for advanced or metastatic cholangiocarcinoma harboring FGFR2 Alterations. AHDB, American Health & Drug Benefits. December 2021. Accessed August 8, 2022.
  4. TRUSELTIQ™ (infigratinib) for the treatment of cholangiocarcinoma. Clinical Trials Arena. June 16, 2021. Accessed August 8, 2022. 
  5. FDA grants accelerated approval to infigratinib for metastatic cholangiocarcinoma. News release. US Food and Drug Administration. May 28, 2021. Accessed August 8, 2022.
  6. Truseltiq (infigratinib). wcg CenterWatch. May 1, 2021. Accessed August 8, 2022.
  7. Riley-Poku Y. Oncology overview: infigratinib for advanced cholangiocarcinoma. Pharmacy Times. August 24, 2021. Accessed August 8, 2022.

Reviewed by Debjyoti Talukdar, MD, on 8/15/2022.