培米替尼的作用与功效及副作用？

Pemigatinib (trade name Pemazyre, code: INCB-054828 or IBI375) is an ATP-competitive and highly selective FGFR-TKI jointly developed by Innovent Biologics and Incyte. The U.S. Food and Drug Administration (FDA) granted it preferential treatment such as "orphan drug", breakthrough treatment results, and priority review designation in 2020. It showed excellent efficacy data in phase II clinical trials and was approved by the FDA's accelerated approval process on April 17, 2020. It is the first and only drug to be used to treat locally advanced or metastatic cholangiocarcinoma with FGFR2 fusion or rearrangement. So, what are the functions, efficacy and side effects of pemetinib?

The role and efficacy of pemetinib

The clinical study FIGHT-202 trial is an open-label, single-arm, multi-center phase II clinical trial (NCTO2924376) designed to evaluate the effectiveness of pemetinib in patients with metastatic/advanced or unresectable cholangiocarcinoma with FGFR2 fusion or rearrangement who have failed at least one treatment. 146 patients were divided into 3 groups: Group A (107 cases, FGFR2 fusion or rearrangement), Group B (20 cases, other FGF/FGFR gene changes), Group C (18 cases, no FGF/FGFR gene changes), and 1 case with undetermined FGF/FGFR gene changes. All patients received pemetinib 13.5 mg qd, with a cycle of 21 days, with 2 weeks of administration and 1 week of drug withdrawal.

The results showed that the objective response rate (ORR) of patients in group A was 36%, including 3 cases of complete response (CR) and 35 cases of partial response (PR), while neither group B nor group C achieved objective response. At an average follow-up time of 15 months, the median progression-free survival (PFS) of group A was 6.9 months, which was higher than the 2.1 months and 1.7 months of groups B and C; the disease control rate (DCR) was 82%, which was higher than the 40% and 22% of groups B and C. The median duration of response in group A was 9.1 months, and the preliminary median overall survival (OS) was 21.1 months, while the OS in groups B and C was only 6.7 months and 4 months.

It is suggested that pemetinib has good efficacy in the treatment of cholangiocarcinoma with FGFR2 fusion or rearrangement, and the efficacy is better than other patients or patients without FGF/FGFR gene alteration.

Pemetinib side effects

Hair loss, dry eyes, diarrhea and dry mouth, separation of nails from the bed or poor nail formation, loss of appetite, vomiting, feeling tired, joint pain, taste changes, pain in the stomach area (abdomen), nausea, low phosphate in the blood, constipation, back pain, mouth ulcers, dry skin, etc.

References

[1] Huang Lu, Tong Ying, Xiong Chuanshuang, Hong Yi. New drug for the treatment of cholangiocarcinoma: fibroblast growth factor receptor 1/2/3 inhibitor pemigatinib [J]. Chinese Journal of New Drugs and Clinics, 2021, 40(07): 503-506. DOI: 10.14109/j.cnki.xyylc.2021.07.05.

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