福巴替尼治疗晚期胆管癌的效果如何？

Forbatinib is effective in treating advanced cholangiocarcinoma and can significantly extend the progression-free period and overall survival rate of patients. In clinical trials, fobatinib has a relatively significant effect in the treatment of advanced cholangiocarcinoma. Phase 3 clinical trial results showed that the patient's overall response rate (ORR) was 42% and the duration of response (DoR) was 9.7 months.

forbatinib

Is a kinase inhibitor used to treat cancer, including cholangiocarcinoma, breast cancer, gastric cancer, urothelial cancer, esophageal cancer, and non-small cell lung cancer.

On September 30, 2022, forbatinib was approved in the United States for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma who carry FGFR2 gene fusions or other rearrangements.

Forbatinib in the treatment of cholangiocarcinoma

Background: Alterations in fibroblast growth factor receptor 2 (FGFR2) have emerged as promising drug targets in intrahepatic cholangiocarcinoma, a rare cancer with poor prognosis. Forbatinib is a next-generation covalently bound FGFR1-4 inhibitor that has demonstrated antitumor activity in patients with FGFR-altered tumors and has strong preclinical activity against acquired resistance mutations associated with ATP-competitive FGFR inhibitors.

Methods: In an open-label, single-arm, phase 2 study, 103 patients with unresectable or metastatic FGFR2 fusion-positive or FGFR2 rearrangement-positive intrahepatic cholangiocarcinoma were recruited to receive oral fortibatinib at a dose of 20 mg once daily.

Study results: A total of 42% of patients responded, with the median duration of response being 9.7 months. After 17.1 months of follow-up, the patients' median progression-free survival was 9 months and overall survival was 21.7 months.

Common treatment-related grade 3 adverse events included hyperphosphatemia, elevated aspartate aminotransferase levels, stomatitis, and fatigue.

Study Conclusions: Use of the covalent FGFR inhibitor fortibatinib provides measurable clinical benefit in patients previously treated for FGFR2 fusion- or rearrangement-positive intrahepatic cholangiocarcinoma.

The effect of forbatinib in the treatment of advanced cholangiocarcinoma

A global, open-label, phase II study, FOENIX-CCA2, showed that in patients with unresectable locally advanced or metastatic iCCA with FGFR2 fusions or rearrangements, treatment with forbatinib resulted in an objective response rate of 37.3%, a median duration of response of 8.3 months, a disease control rate of 82.1%, and a median progression-free survival of 7.2 months.

In one study, TAS-101-20, a multicenter, open-label, single-arm trial, forbatinib was more effective in patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma, with an overall response rate of 95% and a median sustained response time of 7.3 months.

Forbatinib administration

1. Ocular toxicity: Forbatinib can cause retinal pigment epithelial detachment (RPED). Before starting treatment, a comprehensive eye examination including optical coherence tomography (OCT) should be performed every 2 months (first 6 months) and every 3 months thereafter to understand visual symptoms.

2. Hyperphosphatemia and soft tissue mineralization: Elevated phosphate levels can lead to hyperphosphatemia, which can lead to soft tissue mineralization, calcinosis, non-uremic calcinosis, and vascular calcification. Monitor for hyperphosphatemia and discontinue, reduce dose, or permanently discontinue based on duration and severity of hyperphosphatemia.

3. Embryo-embryotoxicity: Forbatinib can cause harm to the fetus. Patients should be informed of the potential reproductive risks and potential risks to the fetus, and use effective contraceptive methods.

Summary

At present, there is no unified standard for the treatment of advanced cholangiocarcinoma. Forbatinib has a certain effect on some patients with cholangiocarcinoma, but the specific treatment effect varies due to individual differences.

References:

Goyal L, Meric-Bernstam F, Hollebecque A, Valle JW, Morizane C, Karasic TB, Abrams TA, Furuse J, Kelley RK, Cassier PA, Klümpen HJ, Chang HM, Chen LT, Tabernero J, Oh DY, Mahipal A, Moehler M, Mitchell EP, Komatsu Y, Masuda K, Ahn D, Epstein RS, Halim AB, Fu Y, Salimi T, Wacheck V, He Y, Liu M, Benhadji KA, Bridgewater JA; FOENIX-CCA2 Study Investigators. Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma. N Engl J Med. 2023 Jan 19;388(3):228-239. doi: 10.1056/NEJMoa2206834. PMID: 36652354.

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