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Futibatinib: A Review in Locally Advanced and Metastatic Cholangiocarcinoma

  • Adis Drug Evaluation
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Abstract

Futibatinib (LYTGOBI®) is an oral small molecule compound that selectively, irreversibly and potently inhibits the tyrosine kinase activity of fibroblast growth factor receptor (FGFR)1–4. It is approved in the EU, Japan and the USA for the treatment of adults with locally advanced or metastatic cholangiocarcinoma (CCA) harbouring an FGFR2 fusion or rearrangement who have progressed following systemic therapy. In the phase II part (FOENIX-CCA2) of a multinational phase I/II study in this patient population, monotherapy with futibatinib 20 mg once daily was associated with clinically meaningful and durable responses, sustained health-related quality of life (HR-QOL), and a manageable safety profile with supportive care and as-needed dose modifications. Indeed, hyperphosphataemia (the most common all grade and grade 3 treatment-related adverse event) was manageable with phosphate-lowering therapy and dose reductions or interruptions. Although further efficacy and tolerability data are expected, current evidence indicates that futibatinib is a valuable targeted therapy option for adults with locally advanced or metastatic CCA harbouring an FGFR2 fusion or rearrangement who have progressed following systemic therapy, a patient population with limited treatment options and poor life expectancy.

Plain Language Summary

Cholangiocarcinoma (CCA) is an invasive tumour arising from the biliary tract. In the early stages it presents silently; this, along with its highly aggressive nature, means it is often diagnosed in the later (advanced) stages when surgery is not a treatment option. Up to half of CCAs have genetic aberrations that can be targeted for treatment. One such abnormality (present in 9–15% of CCAs) is found in fibroblast growth factor receptor (FGFR)2. The presence of this aberration promotes tumour survival and development. Futibatinib (LYTGOBI®) is an oral drug that strongly inhibits the activity of FGFR1–4. When given to adults with unresectable or metastatic CCA harbouring an FGFR2 aberration who had disease progression after systemic therapy, futibatinib 20 mg once daily produced clinically meaningful and prolonged responses and sustained health-related quality of life; moreover, with supportive care and as-needed dose modifications, futibatinib had a manageable safety profile. In a patient population that has limited treatment options and poor life expectancy, current evidence indicates that futibatinib is a valuable targeted therapy option.

Digital Features for this Adis Drug Evaluation can be found at https://doi.org/10.6084/m9.figshare.25468201.

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References

  1. Vogel A, Bridgewater J, Edeline J, et al. Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(2):127–40.

    Article  CAS  PubMed  Google Scholar 

  2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in oncology: biliary tract cancers. Version 3.2023 – November 8, 2023. 2023. https://www.nccn.org/. Accessed 19 Feb 2024.

  3. Rushbrook SM, Kendall TJ, Zen Y, et al. British Society of Gastroenterology guidelines for the diagnosis and management of cholangiocarcinoma. Gut. 2023;73(1):16–46.

    Article  PubMed  Google Scholar 

  4. Banales JM, Marin JJG, Lamarca A, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 2020;17(9):557–88.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Mayo Clinic. Cholangiocarcinoma (bile duct cancer). 2023. https://www.mayoclinic.org/diseases-conditions/cholangiocarcinoma/symptoms-causes/syc-20352408. Accessed 19 Feb 2024.

  6. Javle M, King G, Spencer K, et al. Futibatinib, an irreversible FGFR1-4 inhibitor for the treatment of FGFR-aberrant tumors. Oncologist. 2023;28(11):928–43.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Wekking D, Pretta A, Martella S, et al. Fibroblast growth factor receptors as targets for anticancer therapy in cholangiocarcinomas and urothelial carcinomas. Heliyon. 2023;9(9): e19541.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Taiho Pharma Netherlands B.V. Lytgobi (futibatinib) 4 mg film-coated tablets: EU summary of product characteristics. 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/lytgobi. Accessed 19 Feb 2024.

  9. Taiho Oncology Inc. LYTGOBI® (futibatinib) tablets, for oral use: US prescribing information. 2022. https://www.fda.gov/. Accessed 19 Feb 2024.

  10. Taiho Pharmaceutical Co. Ltd. LYTGOBI® (futibatinib) 4 mg tablets: Japanese prescribing information. 2023. https://www.pmda.go.jp/. Accessed 19 Feb 2024.

  11. Kalyukina M, Yosaatmadja Y, Middleditch MJ, et al. TAS-120 cancer target binding: defining reactivity and revealing the first fibroblast growth factor receptor 1 (FGFR1) irreversible structure. ChemMedChem. 2019;14(4):494–500.

    Article  CAS  PubMed  Google Scholar 

  12. Sootome H, Fujita H, Ito K, et al. Futibatinib is a novel irreversible FGFR 1–4 inhibitor that shows selective antitumor activity against FGFR-deregulated tumors. Cancer Res. 2020;80(22):4986–97.

    Article  CAS  PubMed  Google Scholar 

  13. Valery M, Vasseur D, Fachinetti F, et al. Targetable molecular alterations in the treatment of biliary tract cancers: an overview of the available treatments. Cancers (Basel). 2023;15(18):4446.

    Article  CAS  PubMed  Google Scholar 

  14. Goyal L, Shi L, Liu LY, et al. TAS-120 overcomes resistance to ATP-competitive FGFR inhibitors in patients with FGFR2 fusion-positive intrahepatic cholangiocarcinoma. Cancer Discov. 2019;9(8):1064–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cleary JM, Raghavan S, Wu Q, et al. FGFR2 extracellular domain in-frame deletions are therapeutically targetable genomic alterations that function as oncogenic drivers in cholangiocarcinoma. Cancer Discov. 2021;11(10):2488–505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bahleda R, Meric-Bernstam F, Goyal L, et al. Phase I, first-in-human study of futibatinib, a highly selective, irreversible FGFR1-4 inhibitor in patients with advanced solid tumors. Ann Oncol. 2020;31(10):1405–12.

    Article  CAS  PubMed  Google Scholar 

  17. Hollebecque A, Bridgewater JA, Meric-Bernstam F, et al. Assessment of futibatinib exposure-response (E-R) relationships in patients with advanced solid tumors, including cholangiocarcinoma (CCA) [abstract no. 52P]. Ann Oncol. 2021;32(Suppl 5):S378–9.

    Article  Google Scholar 

  18. Yamamiya I, Lester R, Sonnichsen D, et al. Effect of futibatinib on cardiac repolarization: results of a randomized, controlled, double-blind, QT/QTc, phase 1 study in healthy subjects. Clin Pharmacol Drug Dev. 2023;12(3):304–13.

    Article  CAS  PubMed  Google Scholar 

  19. Yamamiya I, Hunt A, Yamashita F, et al. Evaluation of potential food effects and drug interactions with lansoprazole in healthy adult volunteers receiving futibatinib. Clin Pharmacol Drug Dev. 2023;12(3):294–303.

    Article  CAS  PubMed  Google Scholar 

  20. Yamamiya I, Hunt A, Takenaka T, et al. Evaluation of the cytochrome P450 3A and p-glycoprotein drug-drug interaction potential of futibatinib. Clin Pharmacol Drug Dev. 2023;12(10):966–78.

    Article  CAS  PubMed  Google Scholar 

  21. Gao L, Yamamiya I, Pinti M, et al. A phase I, open-label, single-dose study to evaluate the effect of hepatic impairment on the pharmacokinetics and safety of futibatinib. Clin Transl Sci. 2023;16(9):1713–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Doi T, Shitara K, Kojima T, et al. Phase I study of the irreversible fibroblast growth factor receptor 1–4 inhibitor futibatinib in Japanese patients with advanced solid tumors. Cancer Sci. 2023;114(2):574–85.

    Article  CAS  PubMed  Google Scholar 

  23. Goyal L, Meric-Bernstam F, Hollebecque A, et al. Futibatinib for FGFR2-rearranged intrahepatic cholangiocarcinoma. N Engl J Med. 2023;388(3):228–39.

    Article  CAS  PubMed  Google Scholar 

  24. Bridgewater J, Meric-Bernstam F, Hollebecque A, et al. Efficacy and safety of futibatinib in intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions/other rearrangements: subgroup analyses of a phase II study (FOENIX-CCA2) [abstract no. 54P]. Ann Oncol. 2020;31(Suppl 4):S261–2.

    Article  Google Scholar 

  25. European Medicines Agency. Lytgobi (futibatinib): EU assessment report. 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/lytgobi. Accessed 19 Feb 2024.

  26. US Food and Drug Administration. Futibatinib (Lytgobi): multi‐disciplinary review and evaluation. 2022. https://www.fda.gov/. Accessed 19 Feb 2024.

  27. Goyal L, Meric-Bernstam F, Hollebecque A, et al. Updated results of the FOENIX-CCA2 trial: efficacy and safety of futibatinib in intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions/rearrangements [abstract no. 4009]. J Clin Oncol. 2022;40(16 Suppl).

  28. Borad MJ, Paine A, Wacheck V, et al. Indirect treatment comparison of futibatinib with chemotherapy and pemigatinib in cholangiocarcinoma with FGFR2 fusions/rearrangements [abstract no. 440]. J Clin Oncol. 2022;40(4 Suppl):400.

    Google Scholar 

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Acknowledgments

During the peer review process, the manufacturer of futibatinib 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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    Sheridan M. Hoy

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Correspondence to Sheridan M. Hoy.

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The preparation of this review was not supported by any external funding.

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Sheridan M. Hoy is a salaried employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to this article and are responsible for its content.

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Additional information

The manuscript was reviewed by: M. A. Morse, Division of Medical Oncology, Department of Medicine, Duke University Medical Center and Duke Cancer Institute, Durham, NC, USA; D. Wekking, Location Academic Medical Centre, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

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Hoy, S.M. Futibatinib: A Review in Locally Advanced and Metastatic Cholangiocarcinoma. Targ Oncol 19, 473–480 (2024). https://doi.org/10.1007/s11523-024-01059-8

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