Expert review of anticancer therapy
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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.
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Introduction: Fibroblast growth-factor receptor (FGFR) inhibition is a promising strategy of treatment in urothelial cancer (UC). FGFR3 mutations or fusions (mut/fus) are common in luminal-1 UC subtype, which exhibits poor responses to immunotherapy. Erdafitinib is a potent and selective pan-FGFR tyrosine kinase inhibitor. ⋯ Special attention must be paid to typical adverse class-effects of FGFR inhibitors. In the near future, in order to achieve an optimal selection of molecularly-altered tumors, it will be important to assess the performance of different diagnostic tools and to investigate the role of liquid biopsy. Combinations with immunotherapy represent a novel therapeutic opportunity being tested in ongoing trials.
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Expert Rev Anticancer Ther · Aug 2019
ReviewCapmatinib for the treatment of non-small cell lung cancer.
Introduction: Activation of the MET pathway through MET amplifications or mutations is present in 3-4% of stage IV non-squamous non-small cell lung cancers (NSCLC). High MET amplifications and exon 14 skipping mutations are associated with poor prognosis: new treatments are needed for these patients. Capmatinib is a highly selective, potent small-molecule MET inhibitor with antitumor activity in NSCLC in vitro and in vivo. ⋯ Expert opinion: In the GEOMETRY Mono-1 study, treatment with capmatinib resulted in high response rates in stage IV NSCLC with MET exon 14 skipping mutations, particularly in first line, supporting testing for this biomarker at the time of diagnosis. Durable responses have been reported and results in MET-amplified NSCLC are eagerly anticipated. In EGFR-mutant NSCLC, notable responses have been observed in combination with an EGFR-tyrosine kinase inhibitor (TKI) in case of acquired resistance to EGFR-TKIs based on high MET amplification.