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.
Abbreviations:ASCC (Anal squamous cell carcinoma), FGFR (Fibroblast growth factor receptor)
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- The Fibroblast Growth Factor signaling pathway.WIREs Dev Biol. 2015; 4: 215-266https://doi.org/10.1002/wdev.176
- 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
- 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
- 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
Cancer of the anus, anal canal, and anorectum - cancer stat facts. SEER. Accessed September 27, 2021. https://seer.cancer.gov/statfacts/html/anus.html
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
- 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
- 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
- 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
- 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
- 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
- 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
- Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing.N Engl J Med. 2012; 366: 883-892https://doi.org/10.1056/NEJMoa1113205
- 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
- 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
- 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