Bill Gatton College of Pharmacy, East Tennessee St. University, Johnson City, TN, USA.
J Oncol Pharm Pract. 2021 Apr;27(3):702-710. doi: 10.1177/1078155220983425. Epub 2020 Dec 29.
Comprehensive genomic profiling has an emerging role in cancer therapeutics. As treatment options remain needed for advanced cancers, patients are relying increasingly more on tumor genomic alterations as possible targets for cancer treatment. Frequent tumor fibroblast growth factor receptor (FGFR) alterations are seen in many cancers, and include genetic amplifications, mutations, rearrangements and fusions. FGFR inhibitors target these receptor alterations and show promise as a drug class. Currently 2 medications are currently FDA approved: erdafitinib and pemigatinib. Through the FDA accelerated approval process, erdafitinib is indicated to treat metastatic urothelial carcinoma with FGFR2 and FGFR3 alterations, whereas pemigatinib is indicated to treat unresectable cholangiocarcinoma with FGFR2 alterations. Despite growing knowledge about such advanced cancers, treatment is usually palliative. With multiple FGFR inhibitors in the pipeline, further FDA approvals are possible, and it is likely their role in therapy will extend to other cancer types. This review outlines erdafitinib, pemigatinib, their role in cancer, as well as outlining the possible future use of other FGFR inhibitors in urothelial carcinoma, cholangiocarcinoma, and other malignancies.
全面基因组分析在癌症治疗中具有新兴作用。由于需要更多的治疗方案来治疗晚期癌症，患者越来越依赖肿瘤基因组改变作为癌症治疗的可能靶点。在许多癌症中经常发生成纤维细胞生长因子受体 (FGFR) 的改变，包括基因扩增、突变、重排和融合。FGFR 抑制剂针对这些受体改变，并有望成为一类药物。目前有 2 种药物获得了 FDA 的批准：erdafitinib 和 pemigatinib。通过 FDA 的加速批准程序，erdafitinib 被批准用于治疗具有 FGFR2 和 FGFR3 改变的转移性尿路上皮癌，而 pemigatinib 被批准用于治疗具有 FGFR2 改变的不可切除的胆管癌。尽管对这些晚期癌症有了更多的了解，但治疗通常是姑息性的。随着多种 FGFR 抑制剂在研发中，可能会有更多的 FDA 批准，而且它们在治疗中的作用可能会扩展到其他癌症类型。本文概述了 erdafitinib、pemigatinib，及其在癌症中的作用，以及其他 FGFR 抑制剂在尿路上皮癌、胆管癌和其他恶性肿瘤中的可能未来用途。
