英菲格拉替尼的效果

There is no standard treatment for patients with cholangiocarcinoma who have failed first-line gemcitabine therapy. Fibroblast growth factor receptor 2 (FGFR2) fusions/translocations are present in 13% to 17% of intrahepatic cholangiocarcinomas. Infigratinib is an orally bioavailable, selective pan-FGFR kinase inhibitor that has shown preliminary clinical activity against tumors with FGFR alterations. Trials have shown that infigratinib has significant efficacy and high safety.

A multicenter, open-label phase II study (NCT02150967). Patients received infigratinib 125 mg once daily for 21 days followed by 7 days off (28-day cycle). The primary endpoint was investigator-assessed overall response rate. Results Sixty-one patients (35 women; median age 57 years) with FGFR2 fusions (n ​​= 48), mutations (n ​​= 8), or amplifications (n ​​= 3) participated in the study.

At the prespecified data cutoff point (June 30, 2016), 50 patients discontinued treatment. All responsive tumors contained FGFR2 fusions. The overall effective rate was 14.8% (only 18.8% FGFR2 fusion), the disease control rate was 75.4% (only 83.3% FGFR2 fusion), and the estimated median progression-free survival was 5.8 months.

Infigratinib included hyperphosphatemia (72.1%, all grades), fatigue (36.1%), stomatitis (29.5%), and alopecia (26.2%). Grade 3 or 4 treatment-related adverse events occurred in 25 patients (41%), including hyperphosphatemia (16.4%), stomatitis (6.6%),

Conclusion Infigratinib is a first-in-class FGFR kinase inhibitor with controllable toxicity and shows meaningful clinical activity against chemotherapy-refractory cholangiocarcinoma containing FGFR2 fusions. This promising antitumor activity supports the continued development of infigratinib in this highly selected patient population.

Infigratinib is an orally bioavailable pan-inhibitor of human fibroblast growth factor receptors (FGFRs) with potential anti-angiogenic and anti-tumor activities. Selected for the treatment of patients with unresectable locally advanced or metastatic cholangiocarcinoma based on the presence of FGFR2 fusions or rearrangements. It is recommended that patients take medication under the guidance of a doctor and receive symptomatic treatment.

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References

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