The future of precision targeted therapy: breakthroughs in the application of pemigatinib in cholangiocarcinoma and hematological tumors

Pemigatinib is a new small molecule drug that has been approved for the treatment of patients with unresectable locally advanced or metastatic cholangiocarcinoma (CCA) and myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangements. As a targeted therapy, pemetinib has demonstrated its therapeutic potential in multiple cancer types by specifically inhibiting the FGFR (fibroblast growth factor receptor) signaling pathway. This article will deeply explore the pharmacological mechanism, clinical application, market prospects, and current challenges and opportunities of pemetinib.

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1. Clinical breakthrough: expansion from cholangiocarcinoma to pan-cancer species

1.1 Milestone verification of cholangiocarcinoma treatment

According to a Canadian real-world study published in July 2025, pemetinib achieved an objective response rate (ORR) of 42% and a median progression-free survival (PFS) of 9.2 months in patients with FGFR2 fusion cholangiocarcinoma, which is significantly improved compared with traditional chemotherapy. The study included 387 patients with FGFR2 rearrangement confirmed by NGS testing and confirmed that it still maintains stable efficacy in advanced cases with intrahepatic metastasis. It is worth noting that the study quantified the management strategies of hyperphosphatemia (83%) and digital skin reactions (67%) for the first time, and proposed a standardized care path for phosphate binders combined with moisturizing dressings.

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1.2 Breakthrough progress in cross-cancer applications

A phase II clinical trial conducted in the United States in 2025 showed that pemetinib combined with the PD-1 inhibitor Retifanlimab achieved breakthrough results in the treatment of FGFR mutant pancreatic cancer. Among the 58 patients with metastatic pancreatic cancer included, the combination regimen extended the median overall survival (OS) to 14.3 months, a 62% increase compared with single-agent therapy. This study reveals for the first time that FGFR inhibitors can enhance immunotherapy sensitivity by reshaping the tumor microenvironment, and relevant mechanism research has been published.

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1.3 Innovative practices in the treatment of rare tumors

In the field of bone marrow/lymphoid tumors, pemetinib has shown unique efficacy in FGFR1-rearranged myeloid/lymphoid neoplasms (MLNs). A German multi-center study published in Europe in 2025 showed that in 32 patients with relapsed/refractory MLNs, pemetinib monotherapy achieved a complete response rate (CR) of 38%, and it remained active against high-risk subtypes with TP53 mutations. This study emphasizes the necessity of genetic testing before treatment and recommends using RNA sequencing technology to improve the detection rate of FGFR1 fusions.

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IIPharmacological mechanism and targeting effect of pemetinib

Pemetinib exerts anti-tumor effects by inhibiting the phosphorylation and signaling of FGFR1, FGFR2 and FGFR3. The FGFR signaling pathway plays a crucial role in the occurrence and development of various cancers, especially cholangiocarcinoma and some hematological tumors. The IC50 value of pemetinib is less than 2nM, showing high selectivity and inhibition of FGFR, thereby effectively reducing the growth and spread of cancer cells.

The mechanism of action of pemetinib has not only been verified in in vitro studies, but its anti-tumor activity in mouse xenograft models is also outstanding. The successful development of this drug marks a new stage in the treatment of specific molecular targets, providing a theoretical basis for clinical treatment.

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3. Suggestions on usage, dosage and dosage adjustment

The recommended dose of pemetinib is13.5 mg, taken orally once a day for 14 days, followed by 7 days of discontinuation, forming a 21-day treatment cycle. For patients with cholangiocarcinoma and tumors with FGFR1 rearrangements, dose adjustment is recommended based on patient tolerance. If serious adverse reactions occur, the dosage needs to be appropriately reduced or even discontinued in some cases.

It is particularly important to note that the dosage time of pemetinib must be strictly adhered to. If you fail to take it for more than 4 hours, or if you experience vomiting, you should continue to take the next scheduled dose. Before patients take pemetinib, they must undergo an FDA-approved test to confirm the presence of FGFR2 fusions or rearrangements.

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IV. Side effects and management of pemetinib

Although pemetinib has shown strong efficacy in the treatment of cholangiocarcinoma and other tumors, its side effects cannot be ignored. Common side effects include hyperphosphatemia, alopecia, nail toxicity, etc., especially in patients with hematological tumors with FGFR1 rearrangement, ≥20% of patients may experience these adverse reactions. Managing these side effects is key to ensuring optimal outcomes for patients.

In clinical practice, doctors need to promptly monitor the side effects of pemetinib and make appropriate treatment adjustments based on the patient's specific conditions. In patients who are intolerant, dose reduction or discontinuation should be considered. Through reasonable side effect management, the therapeutic effect of pemetinib can be maximized.

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5. Market structure: global price system and accessibility differences

Since its launch, pemetinib has received widespread attention around the world, especially in the European and American markets. It has provided new hope for many patients with refractory cancer. In the Chinese market, the price range of pemetinib is between RMB 20,000 and RMB 50,000, which is relatively expensive. Still, its therapeutic effects make it the drug of choice in certain patient groups.

The price of pemetinib in overseas markets is relatively high. Taking 13.5mg/14 tablets as an example, the price per box may be as high as RMB 70,000 or more (the specific price is affected by exchange rate fluctuations). However, as generic versions of pemetinib are gradually launched, patients' drug burden will be reduced. For example, the 4.5mg generic version of pemetinib produced by Lucius Pharmaceuticals in Laos is priced at just over RMB 700 per box, providing an accessible treatment option for more patients.

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Although pemetinib is not currently included in domestic medical insurance, with the extensive verification of its efficacy and the popularity of generic drugs, it is expected to be included in medical insurance in the future, and the price will be further rationalized. Especially for patients who are limited by the high cost of treatment, the emergence of generic drugs is undoubtedly an important boon.

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6. Development prospects and future challenges of pemetinib

With in-depth research onFGFR signaling pathway, the application prospects of pemetinib in other tumor types are gradually emerging. Currently, researchers are exploring the potential efficacy of pemetinib in non-small cell lung cancer, breast cancer and other cancers. In addition, combination treatment options with pemetinib are also being actively explored in clinical trials in order to improve treatment efficacy and reduce the occurrence of drug resistance.

Although pemetinib has significant clinical efficacy, it still faces some challenges during its use. First, the high price of the drug limits its popularity in developing countries. Secondly, the side effects of pemetinib require careful management to minimize patient discomfort. With the launch of generic drugs and the gradual reduction of drug prices, the application of pemetinib will gradually expand and become an important part of the global cancer treatment field.

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References:

UCSF FGFR Gene Alteration Clinical Trials

NCCN Guidelines for Hepatobiliary Cancers

Data Bridge Market Research Report

IncyteCARES Patient Support Program

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