培米替尼(Pemazyre)治疗胆管癌的效果如何？

According to research data, the use of targeted drugs (pemigatinib, Pemazyre) to treat patients with intrahepatic cholangiocarcinoma has shown significant efficacy. Research shows that this treatment has an objective response rate of 35.5% and a disease control rate of 82%. Additionally, the median duration of response was 9.1 months, with 63% of patients experiencing a response lasting 6 months or longer, and 18% experiencing a response lasting 12 months or longer.

About pemetinib

Pemetinib (Pemazyre) is a selective FGFR tyrosine kinase inhibitor jointly developed by Innovent Biologics and Incyte. It was approved by the U.S. Food and Drug Administration (FDA) under the accelerated approval process on April 17, 2020, for the treatment of

It is used to treat locally advanced or metastatic cholangiocarcinoma with FGFR2 fusion or rearrangement. The drug is marketed as tablets with three specifications. Each tablet contains 4.5 mg, 9 mg, and 13.5 mg of active ingredients. Additives or excipients include magnesium stearate, microcrystalline cellulose, and sodium methyl starch.

The role of pemetinib

Pemetinib selectively inhibits the growth of tumor cells by inhibiting FGFR1-3 phosphorylation and signaling processes, blocking the constitutive activation of FGFR signaling caused by FGFR amplification and fusion. Preclinical studies have shown that pemetinib exhibits good anti-tumor activity against FGFR1~3 mutated tumor cells in cell line models and mouse human tumor xenograft models.

The therapeutic effect of pemetinib

FIGHT-202 (NCTO2924376) is an open-label, multi-center phase II study [1] that mainly evaluates the safety and efficacy of pemigatinib in patients with locally advanced or metastatic cholangiocarcinoma who have failed previous treatments. A total of 146 patients were included in the trial, with a median age of 59 years (range 26 to 78 years), 42% were female and 58% were male. 126 patients (86%) had metastatic disease and 57 patients (39%) had received two or more treatments.

The trial is divided into 3 cohorts. Cohort A is for patients with FGFR2 fusion or rearrangement (n=107), cohort B is for patients with FGF/FGFR genetic changes (n=20), cohort C is for patients without FGF/FGFR genetic changes (n=18), and the remaining 1 patient is undecided. All patients received pemigatinib 13.5 mg (po, qd), a 3-week course of treatment (2 weeks of administration followed by 1 week of discontinuation) until radiological examination showed progression or intolerable toxicity. The primary endpoint was ORR in cohort A, and secondary endpoints were progression-free survival (PFS), disease control rate (DCR), duration of response (DOR), and overall survival (OS).

The trial results showed that the ORR of patients in cohort A was 35.5% (n=38), of which 3 patients achieved complete response (CR), 35 patients achieved PR, and 88 patients had effective disease control. The DCR was 82%, the DOR was 7.5 months (95% CI: 57~14.5), the PFS was 6.9 months (95% CI: 6.2~9.6), and the OS was 21.1 months: Cohort The ORR for cohort B and cohort C was 0%. Compared with the other two cohorts, the survival time of patients in Cohort A was significantly longer, indicating that pemigatinib has a good therapeutic effect on patients with cholangiocarcinoma with FGFR2 fusion or rearrangement.

Summary

Pemigatini is the first targeted therapy for cholangiocarcinoma approved by the US FDA. It can inhibit FGFR tyrosine kinase and has a good therapeutic effect on cholangiocarcinoma with FGFR fusion or rearrangement. The adverse reactions are controllable and can be tolerated by patients. At the same time, clinical trials of pemigatinib against bladder cancer (NCTO3914794), urothelial cancer [NCTO2872714 (FIGHT 201), NCT04003610 (FIGHT 205)], colorectal cancer (NCTO4096417), and myeloproliferative tumors [NCTO3011372 (FIGHT 203)] are ongoing, showing broad application prospects.

References

[1]ARAI Y.TOTOKI Y,HOSODA F,et al. Fibroblast growth fac-tor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma [J].Hepatology, 2014, 59(4):1427-1434.D0I: 10.1002/hep.26890.

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