Global Expanded Access Program for Pemigatinib in Patients with Previously Treated Locally Advanced or Metastatic Cholangiocarcinoma and Fibroblast Growth Factor Receptor Gene Alterations

Overview

Journal Cancer Res Treat

Specialty Oncology

Date 2024 Feb 14

PMID 38351684

Authors

Anouk Lindley

Gerald Prager

Michael Bitzer

Timothy C Burn

Christine F Lihou

Elisabeth Croft

Affiliations

Soon will be listed here.

Abstract

Purpose: Pemigatinib is a fibroblast growth factor receptor-2 (FGFR2) inhibitor approved for use in patients with previously treated cholangiocarcinoma (CCA) and FGFR2 fusions or rearrangements. This ongoing global Expanded Access Program (EAP) allows physicians in regions where pemigatinib is not commercially available to request pemigatinib for patients with locally advanced or metastatic CCA who, in the physician's opinion, could benefit from pemigatinib treatment.

Materials And Methods: Eighty-nine patients from Europe, North America, and Israel were treated from January 2020 through September 2021.

Results: Patients had FGFR gene fusions (68.5%), rearrangements (12.4%), translocations (5.6%), amplifications (2.2%), and other alterations (11.2%). Median duration of treatment in the EAP was 4.0 months (range, 0.1 to 13.6 months). The most frequently reported adverse event (AE) was hyperphosphatemia (22.5%); the most common serious AE was cholangitis (3.4%). Treatment discontinuation was associated with reports of AEs for seven patients (7.9%). AEs associated with pemigatinib were consistent with those observed in clinical trials.

Conclusion: Efficacy was not assessed in this EAP. However, some patients remained on treatment for up to a year, suggesting that they observed a benefit from treatment. Patients with CCA should undergo molecular testing to identify those who could benefit from targeted treatments such as pemigatinib.

References

Lowery M, Goff L, Keenan B, Jordan E, Wang R, Bocobo A . Second-line chemotherapy in advanced biliary cancers: A retrospective, multicenter analysis of outcomes. Cancer. 2019; 125(24):4426-4434. PMC: 8172082. DOI: 10.1002/cncr.32463. View

Arai Y, Totoki Y, Hosoda F, Shirota T, Hama N, Nakamura H . Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma. Hepatology. 2013; 59(4):1427-34. DOI: 10.1002/hep.26890. View

Liu P, Koblish H, Wu L, Bowman K, Diamond S, DiMatteo D . INCB054828 (pemigatinib), a potent and selective inhibitor of fibroblast growth factor receptors 1, 2, and 3, displays activity against genetically defined tumor models. PLoS One. 2020; 15(4):e0231877. PMC: 7313537. DOI: 10.1371/journal.pone.0231877. View

Louis C, Papoutsoglou P, Coulouarn C . Molecular classification of cholangiocarcinoma. Curr Opin Gastroenterol. 2020; 36(2):57-62. DOI: 10.1097/MOG.0000000000000611. View

Vogel A, Bridgewater J, Edeline J, Kelley R, Klumpen H, Malka D . Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022; 34(2):127-140. DOI: 10.1016/j.annonc.2022.10.506. View

Amini N, Ejaz A, Spolverato G, Kim Y, Herman J, Pawlik T . Temporal trends in liver-directed therapy of patients with intrahepatic cholangiocarcinoma in the United States: a population-based analysis. J Surg Oncol. 2014; 110(2):163-70. DOI: 10.1002/jso.23605. View

Abou-Alfa G, Sahai V, Hollebecque A, Vaccaro G, Melisi D, Al-Rajabi R . Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020; 21(5):671-684. PMC: 8461541. DOI: 10.1016/S1470-2045(20)30109-1. View

Oh D, Lee K, Lee D, Yoon J, Kim T, Bang J . Gemcitabine and cisplatin plus durvalumab with or without tremelimumab in chemotherapy-naive patients with advanced biliary tract cancer: an open-label, single-centre, phase 2 study. Lancet Gastroenterol Hepatol. 2022; 7(6):522-532. DOI: 10.1016/S2468-1253(22)00043-7. View

Javle M, Lee S, Azad N, Borad M, Kelley R, Sivaraman S . Temporal Changes in Cholangiocarcinoma Incidence and Mortality in the United States from 2001 to 2017. Oncologist. 2022; 27(10):874-883. PMC: 9526482. DOI: 10.1093/oncolo/oyac150. View

10.

Rumgay H, Ferlay J, de Martel C, Georges D, Ibrahim A, Zheng R . Global, regional and national burden of primary liver cancer by subtype. Eur J Cancer. 2021; 161:108-118. DOI: 10.1016/j.ejca.2021.11.023. View

11.

Kommalapati A, Tella S, Borad M, Javle M, Mahipal A . FGFR Inhibitors in Oncology: Insight on the Management of Toxicities in Clinical Practice. Cancers (Basel). 2021; 13(12). PMC: 8231807. DOI: 10.3390/cancers13122968. View

12.

Spolverato G, Kim Y, Alexandrescu S, Marques H, Lamelas J, Aldrighetti L . Management and Outcomes of Patients with Recurrent Intrahepatic Cholangiocarcinoma Following Previous Curative-Intent Surgical Resection. Ann Surg Oncol. 2015; 23(1):235-43. DOI: 10.1245/s10434-015-4642-9. View

13.

Lowery M, Ptashkin R, Jordan E, Berger M, Zehir A, Capanu M . Comprehensive Molecular Profiling of Intrahepatic and Extrahepatic Cholangiocarcinomas: Potential Targets for Intervention. Clin Cancer Res. 2018; 24(17):4154-4161. PMC: 6642361. DOI: 10.1158/1078-0432.CCR-18-0078. View

14.

Subbiah V, Iannotti N, Gutierrez M, Smith D, Feliz L, Lihou C . FIGHT-101, a first-in-human study of potent and selective FGFR 1-3 inhibitor pemigatinib in pan-cancer patients with FGF/FGFR alterations and advanced malignancies. Ann Oncol. 2022; 33(5):522-533. DOI: 10.1016/j.annonc.2022.02.001. View

15.

Jain A, Borad M, Kelley R, Wang Y, Abdel-Wahab R, Meric-Bernstam F . Cholangiocarcinoma With Genetic Aberrations: A Unique Clinical Phenotype. JCO Precis Oncol. 2022; 2:1-12. DOI: 10.1200/PO.17.00080. View