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.
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Expert Rev Anticancer Ther · Apr 2020
ReviewLorlatinib for the treatment of ALK-positive metastatic non-small cell lung cancer.
Introduction: The treatment of lung cancer has changed dramatically with the development of tyrosine kinase inhibitors (TKIs) that target sensitizing somatic (gene) activations including anaplastic lymphoma kinase (ALK)-rearrangements. Despite remarkable initial responses, patients develop progressive disease via various resistance mechanisms, some of which are ALK dependent. Various next-generation ALK TKIs have been developed to improve on central nervous system (CNS) activity and also target the multitude of acquired resistance mechanisms. ⋯ Expert opinion: Patients invariably develop resistance during treatment with lorlatinib. Unique combinations of ALK resistance mutations may confer sensitivity to alternate ALK TKIs. There is a move toward individualized biomarker-driven treatment strategies to identify the select group of candidates that can benefit from existing therapies.
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Expert Rev Anticancer Ther · Nov 2019
ReviewElotuzumab in combination with pomalidomide and dexamethasone for the treatment of multiple myeloma.
Introduction: Despite major advances in the therapeutic management of multiple myeloma (MM), it remains an incurable disease. Several combinations of monoclonal antibodies with novel agents are being investigated with promising results in order to prolong progression-free and overall survival. ⋯ These regimens seem to be more effective than the standard combination of pomalidomide with dexamethasone alone. Taking into consideration that the vast majority of MM patients will receive upfront treatment including a PI and lenalidomide in the near future, pomalidomide-based triplets, such as elotuzumab-pomalidomide-dexamethasone, will become the standard of care in the second line of therapy.