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Targeted Fibroblast Growth Factor Receptor (FGFR) Inhibition in Recurrent, Metastatic Anal Carcinoma: A Case Report

Published:January 20, 2022DOI:https://doi.org/10.1016/j.clcc.2022.01.001

      Clinical Practice Points

      • This report describes a patient with recurrent, metastatic anal squamous cell carcinoma (ASCC) who failed multiple lines of therapy followed by an impressive response to pemigatinib, an oral inhibitor of FGFR1, 2, and 3.
      • This case demonstrates how mutational analysis in the setting of advanced disease may elucidate actionable mutations when standard therapies have been exhausted.
      • Targeted FGFR inhibition may provide benefit to patients with advanced, refractory, FGFR-aberrant ASCC. Randomized trials would be helpful to better describe efficacy and durability of response.

      Keywords

      Abbreviations:

      ASCC (Anal squamous cell carcinoma), FGFR (Fibroblast growth factor receptor)
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      References

        • Ornitz DM
        • Itoh N.
        The Fibroblast Growth Factor signaling pathway.
        WIREs Dev Biol. 2015; 4: 215-266https://doi.org/10.1002/wdev.176
        • Porta R
        • Borea R
        • Coelho A
        • et al.
        FGFR a promising druggable target in cancer: molecular biology and new drugs.
        Crit Rev Oncol Hematol. 2017; 113: 256-267https://doi.org/10.1016/j.critrevonc.2017.02.018
        • Helsten T
        • Elkin S
        • Arthur E
        • Tomson BN
        • Carter J
        • Kurzrock R
        The FGFR landscape in cancer: analysis of 4,853 tumors by next-generation sequencing.
        Clin Cancer Res. 2016; 22: 259-267https://doi.org/10.1158/1078-0432.CCR-14-3212
        • Facchinetti F
        • Hollebecque A
        • Bahleda R
        • et al.
        Facts and new hopes on selective FGFR inhibitors in solid tumors.
        Clin Cancer Res Off J Am Assoc Cancer Res. 2020; 26: 764-774https://doi.org/10.1158/1078-0432.CCR-19-2035
      1. Cancer of the anus, anal canal, and anorectum - cancer stat facts. SEER. Accessed September 27, 2021. https://seer.cancer.gov/statfacts/html/anus.html

      2. Anal cancer mortality statistics. Cancer Research UK. Published May 14, 2015. Accessed September 27, 2021. https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/anal-cancer/mortality

        • Chung JH
        • Sanford E
        • Johnson A
        • et al.
        Comprehensive genomic profiling of anal squamous cell carcinoma reveals distinct genomically defined classes.
        Ann Oncol. 2016; 27: 1336-1341https://doi.org/10.1093/annonc/mdw152
        • Abou-Alfa GK
        • Sahai V
        • Hollebecque A
        • et al.
        Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study.
        Lancet Oncol. 2020; 21: 671-684https://doi.org/10.1016/S1470-2045(20)30109-1
        • Morris VK
        • Salem ME
        • Nimeiri H
        • et al.
        Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study.
        Lancet Oncol. 2017; 18: 446-453https://doi.org/10.1016/S1470-2045(17)30104-3
        • Marabelle A
        • Le DT
        • Ascierto PA
        • et al.
        Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair–Deficient Cancer: Results From the Phase II KEYNOTE-158 Study.
        J Clin Oncol. 2020; 38: 1-10https://doi.org/10.1200/JCO.19.02105
        • Kim HR
        • Kim DJ
        • Kang DR
        • et al.
        Fibroblast growth factor receptor 1 gene amplification is associated with poor survival and cigarette smoking dosage in patients with resected squamous cell lung cancer.
        J Clin Oncol Off J Am Soc Clin Oncol. 2013; 31: 731-737https://doi.org/10.1200/JCO.2012.43.8622
        • Chang J
        • Liu X
        • Wang S
        • et al.
        Prognostic Value of FGFR Gene Amplification in Patients with Different Types of Cancer: A Systematic Review and Meta-Analysis. Härkönen PL.
        PLoS ONE. 2014; 9e105524https://doi.org/10.1371/journal.pone.0105524
        • Gerlinger M
        • Rowan AJ
        • Horswell S
        • et al.
        Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing.
        N Engl J Med. 2012; 366: 883-892https://doi.org/10.1056/NEJMoa1113205
        • Lanman RB
        • Mortimer SA
        • Zill OA
        • et al.
        Analytical and Clinical Validation of a Digital Sequencing Panel for Quantitative, Highly Accurate Evaluation of Cell-Free Circulating Tumor DNA.
        PLoS ONE. 2015; 10e0140712https://doi.org/10.1371/journal.pone.0140712
        • Walker F
        • Abramowitz L
        • Benabderrahmane D
        • et al.
        Growth factor receptor expression in anal squamous lesions: modifications associated with oncogenic human papillomavirus and human immunodeficiency virus.
        Hum Pathol. 2009; 40: 1517-1527https://doi.org/10.1016/j.humpath.2009.05.010
        • Palakurthi S
        • Kuraguchi M
        • Zacharek SJ
        • et al.
        The combined effect of FGFR inhibition and PD-1 blockade promotes tumor-intrinsic induction of antitumor immunity.
        Cancer Immunol Res. 2019; 7: 1457-1471https://doi.org/10.1158/2326-6066.CIR-18-0595