Expert review of anticancer therapy
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Expert Rev Anticancer Ther · Sep 2020
ReviewCombination therapy in advanced urothelial cancer: the role of PARP, HER-2 and mTOR inhibitors.
Despite significant advances in the treatment of metastatic urothelial carcinoma, including the advent of immune checkpoint inhibitors, this disease is still challenging to treat and associated poor outcomes remain. Genomic characterization of advanced-stage urothelial carcinoma is widening the field of potential treatments due to the identification of novel biologic drivers. ⋯ Several challenges need to be faced in the development of new potential therapeutic strategies, such as inter/intratumoral heterogeneity and the lack of validated biomarkers.
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Expert Rev Anticancer Ther · Jul 2020
ReviewThe emerging role of antibody-drug conjugates in urothelial carcinoma.
In December 2019, the US Food and Drug Administration granted accelerated approval to the novel nectin-4-targeting antibody-drug conjugate, enfortumab vedotin, for the treatment of platinum-refractory and immune checkpoint blockade-refractory locally advanced or metastatic urothelial carcinoma. Antibody-drug conjugates represent a new therapeutic modality in urothelial cancer; and beyond nectin-4, agents targeting Trop-2, HER2, and EpCAM are also in clinical development. ⋯ The high response rates observed with enfortumab vedotin - both as monotherapy and in combination with checkpoint blockade immunotherapy - suggest this and other antibody-drug conjugates may have efficacy similar to or even exceeding that of traditional cytotoxic chemotherapy. Ongoing clinical development of antibody-drug conjugates in urothelial cancer will address the optimal combination or sequencing strategy with anti-PD-1/L1 immunotherapy and platinum-based chemotherapy.
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Expert Rev Anticancer Ther · Jun 2020
ReviewUrothelial carcinoma: the development of FGFR inhibitors in combination with immune checkpoint inhibitors.
The recent approval of erdafitinib and the emergence of other potent and selective fibroblast growth factor receptor (FGFR) inhibitors (FGFRi's) are shifting the treatment paradigm for patients with advanced urothelial carcinoma (UC) harboring FGFR3 alterations. Whether such therapies can, and should, be combined with immune checkpoint inhibitors (ICI's) is an area of major research interest. ⋯ However, FGFR3 altered tumors may exhibit distinct immunobiology compared with WT tumors that could potentially be exploited therapeutically. Given these considerations along with the clinical non-cross resistance of these therapeutic classes, clinical investigation of regimens combining FGFR3i and ICI is warranted.