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Pemigatinib: A Review in Advanced Cholangiocarcinoma

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Abstract

Pemigatinib (Pemazyre®), a selective, potent, reversible, oral inhibitor of fibroblast growth factor receptor (FGFR) 1–3, has received conditional (in the EU) or accelerated (in the USA) approval for the treatment of adults with previously treated, unresectable locally-advanced or metastatic cholangiocarcinoma (CCA) with an FGFR2 gene fusion or rearrangement. Over the course of a single-arm, phase 2 study (FIGHT-202), just over a third of patients with pretreated, advanced CCA [almost exclusively intrahepatic CCA (iCCA)] harbouring an FGFR2 fusion or rearrangement who received pemigatinib once daily (2 weeks on, 1 week off) had an objective response; nearly half had stable disease. Median progression-free survival and overall survival at the time of the final analysis were 7.0 months and 17.5 months, respectively. Pemigatinib was generally well tolerated and had a manageable safety profile. The most common treatment-related adverse event, hyperphosphataemia, was exclusively grade 1–2 in severity and, similarly, observed ocular and nail toxicities were rarely grade ≥ 3 in severity. Pending confirmation of its clinical benefits in an ongoing cisplatin plus gemcitabine-controlled, phase 3 study (FIGHT-302), pemigatinib provides a valuable targeted therapy for pretreated patients with advanced (i)CCA harbouring a FGFR2 fusion or rearrangement.

Plain Language Summary

Bile duct cancer or cholangiocarcinoma (CCA) has a very poor prognosis, partly because the majority of patients are first diagnosed at an advanced stage when they are no longer eligible for potentially curative surgery and are therefore limited to receiving systemic (palliative) chemotherapy, which results in only modest survival gains. 10–20% of CCAs arise inside the liver [intrahepatic CCAs (iCCAs)]; ≈ 10–20% of patients with advanced iCCAs are eligible to receive fibroblast growth factor receptors (FGFR) inhibitors, as the development of their tumours depends, in part, on FGFRs that have been inappropriately activated due to underlying genetic abnormalities. Pemigatinib (Pemazyre®) is a selective, potent, once-daily oral FGFR 1–3 inhibitor. In a phase 2 trial in patients with advanced CCA (almost exclusively iCCA) containing an abnormal FGFR2 fusion or rearrangement who had already received systemic chemotherapy, more than a third receiving pemigatinib experienced partial or complete shrinkage of their tumours, while almost half had neither growth nor shrinkage of their tumours. Pemigatinib was generally well tolerated with a manageable safety profile. Pending completion of a phase 3 study designed to confirm its clinical benefits, pemigatinib represents a valuable targeted therapy for pretreated patients with advanced (i)CCA harbouring a FGFR2 fusion or rearrangement.

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Acknowledgements

During the peer review process, the manufacturer of pemigatinib was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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    James E. Frampton

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  1. James E. Frampton
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James E. Frampton is a salaried employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

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The manuscript was reviewed by: C. Hierro, Medical Oncology Department. Catalan Institute of Oncology-Badalona, Badalona-Applied Research Group in Oncology (B-ARGO), Badalona, Barcelona, Spain; M. A. Morse, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.

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Frampton, J.E. Pemigatinib: A Review in Advanced Cholangiocarcinoma. Targ Oncol 19, 107–114 (2024). https://doi.org/10.1007/s11523-023-01024-x

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