Casadei Chiara, Dizman Nazli, Schepisi Giuseppe, Cursano Maria Concetta, Basso Umberto, Santini Daniele, Pal Sumanta K, De Giorgi Ugo
Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Ther Adv Med Oncol. 2019 Nov 25;11:1758835919890285. doi: 10.1177/1758835919890285. eCollection 2019.
Inhibitors of fibroblast growth factor receptor (FGFR) represent an outstanding treatment approach for selected patients with urothelial cancer (UC). These agents are changing the clinical approach to a subgroup of UC, the luminal-papillary subtype, characterized by FGFR mutations, fusions, or amplification. In this review, we provide an overview of the results of recent clinical trials on FGFR tyrosine kinase inhibitors (TKIs) currently in clinical development for the treatment of UC: erdafitinib, rogaratinib, infigratinib, and the monoclonal antibody vofatamab. The Food and Drug Administration recently granted accelerated approval to erdafitinib for patients with advanced UC with alterations of FGFR2 or FGFR3 after progression on platinum-based chemotherapy. We also look at future therapeutic options of combination regimens with immune-checkpoint inhibitors as strategies for improving the antitumor effects of this class of drug, and for preventing or delaying the development of resistance.
成纤维细胞生长因子受体(FGFR)抑制剂是治疗特定尿路上皮癌(UC)患者的一种出色治疗方法。这些药物正在改变对UC的一个亚组即腔乳头状亚型的临床治疗方法,该亚型的特征是FGFR突变、融合或扩增。在本综述中,我们概述了目前正在临床开发中用于治疗UC的FGFR酪氨酸激酶抑制剂(TKIs)的近期临床试验结果:厄达替尼、罗加替尼、英菲格拉替尼以及单克隆抗体沃法他单抗。美国食品药品监督管理局最近加速批准厄达替尼用于铂类化疗进展后出现FGFR2或FGFR3改变的晚期UC患者。我们还探讨了联合免疫检查点抑制剂方案作为改善这类药物抗肿瘤效果以及预防或延缓耐药性发展策略的未来治疗选择。