培米替尼适合所有胆管癌患者吗？

Pemetinib is not suitable for all patients with cholangiocarcinoma. Pemetinib is indicated for the treatment of adult patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma treated with fibroblast growth factor receptor 2 (FGFR2) fusions or other rearrangements.

Indications of pemetinib

Also known as pemetinib, the indication is for the treatment of adult patients with advanced, metastatic or unresectable cholangiocarcinoma who have received at least one systemic therapy in the past and have been confirmed to have FGFR2 fusion or rearrangement. It is not suitable for all patients with cholangiocarcinoma.

The mechanism of action of pemetinib

Pemetinib is a potent and selective small molecule oral inhibitor of FGFR1/2/3. Its mechanism of action is to prevent the growth and spread of tumors by inhibiting the activity of FGFR (fibroblast growth factor receptor). FGFR2 fusion or rearrangement is a specific molecular marker in cholangiocarcinoma, and not all cholangiocarcinoma patients will detect this genetic mutation.

Pemetinib is not suitable for all patients with cholangiocarcinoma

Only patients with FGFR2 fusion or rearrangement in the tumor cells of cholangiocarcinoma may benefit from pemetinib treatment and can be treated with this drug. Before starting pemetinib, doctors usually order molecular testing to confirm the presence of FGFR2 fusions or rearrangements.

For patients with cholangiocarcinoma without FGFR2 fusion or rearrangement, pemetinib may not be effective, so they cannot take this drug for treatment. They need to choose other treatment options, such as chemotherapy, targeted therapy, immunotherapy or supportive therapy. The specific treatment plan should be decided by the doctor based on the patient's specific situation.

Efficacy of pemetinib

Research background

Fibroblast growth factor receptor (FGFR) 2 gene alterations are related to the onset of cholangiocarcinoma. Pemetinib is a selective and potent oral inhibitor of FGFR1, 2 and 3. This study evaluated the safety and antitumor activity of pemetinib in patients with previously treated locally advanced or metastatic cholangiocarcinoma, with or without FGFR2 fusions or rearrangements.

Research Methods

In a multicenter, open-label, single-arm, multi-short, phase 2 study, 146 patients aged 18 years or older with disease progression who had received at least one prior treatment and had FGFR2 fusion or rearrangement, other FGF/FGFR mutations, or no FGF/FGFR mutations were enrolled.

Patients received pemmetantide at an initial dose of 13 ± 5 mg once daily until disease progression, unacceptable toxicity, withdrawal of consent, or physician decision.

Results

After a median follow-up of 17.8 months, 35.5% of patients with FGF R2 fusion or rearrangement achieved objective response. Pemetinib has therapeutic potential in patients with cholangiocarcinoma who have previously received FGFR2 fusion or rearrangement.

Summary

Shows survival benefit in second-line treatment of CCA refractory to FGFR2 fusion or rearrangement. If you have cholangiocarcinoma and need to be treated with pemetinib, you need to undergo genetic testing with an FDA-approved testing method. Only after meeting the drug indications can you use this drug for treatment under the guidance of a doctor. Please follow the doctor's instructions for usage and dosage.

References:

Abou-Alfa GK, Sahai V, Hollebecque A, Vaccaro G, Melisi D, Al-Rajabi R, Paulson AS, Borad MJ, Gallinson D, Murphy AG, Oh DY, Dotan E, Catenacci DV, Van Cutsem E, Ji T, Lihou CF, Zhen H, Féliz L, Vogel A. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020 May;21(5):671-684. doi: 10.1016/S1470-2045(20)30109-1. Epub 2020 Mar 20. Erratum in: Lancet Oncol. 2024 Jan;25(1):e3. PMID: 32203698; PMCID: PMC8461541.

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