Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Expert Rev Clin Pharmacol. 2020 Jan;13(1):1-6. doi: 10.1080/17512433.2020.1702025. Epub 2019 Dec 22.
: Since the approval of immune checkpoint inhibitors (ICIs), there has been continuing and significant progress in urothelial cancer (UC) treatment. However, only about one fifth of UC patients respond to ICI. Recently, erdafitinib was developed for treating locally advanced or metastatic UC (mUC) with alterations, accounting for 15-20% of patients. Erdafitinib is the first targeted therapy ever approved for mUC.: This review summarizes the preclinical and clinical data on erdafitinib for UC. PubMed search and relevant articles presented at international conferences were used for the literature search.: The FDA approval of erdafitinib provided a new treatment option for -altered UC progressing on platinum-based chemotherapy. It is not clear whether FGFR inhibitor is a preferred second-line treatment choice to ICI. Compared to ICI, erdafitinib has a better response rate in patients with visceral metastases. However, a shorter duration of response and toxicity profile of erdafitinib, particularly ocular toxicity, is an important consideration. Regular eye exams are recommended by the FDA. Tumor profiling during upfront therapy may help identify those who benefit at the time of progression. In summary, a high unmet need remains for new drugs in chemotherapy- and ICI-refractory UC.
: 自免疫检查点抑制剂(ICI)获得批准以来,尿路上皮癌(UC)的治疗不断取得重大进展。然而,只有约五分之一的 UC 患者对 ICI 有反应。最近,erdafitinib 被开发用于治疗局部晚期或转移性 UC(mUC),其特征在于 15-20%的患者存在改变。erdafitinib 是首个获批用于 mUC 的靶向治疗药物。
: 本综述总结了 erdafitinib 治疗 UC 的临床前和临床数据。使用 PubMed 搜索和国际会议上提交的相关文章进行文献检索。
: FDA 批准 erdafitinib 为在铂类化疗后进展的 FGFR 改变的 UC 提供了新的治疗选择。FGFR 抑制剂是否是 ICI 的首选二线治疗选择尚不清楚。与 ICI 相比,erdafitinib 在有内脏转移的患者中具有更高的缓解率。然而,erdafitinib 的反应持续时间较短,且毒性谱,尤其是眼部毒性,是一个重要的考虑因素。FDA 建议定期进行眼部检查。在一线治疗期间进行肿瘤分析可能有助于确定在进展时受益的患者。综上所述,在化疗和 ICI 难治性 UC 中,仍存在很大的未满足的药物需求。