title: Single-Agent Therapies After Standard Combination Regimens.
abstract: Increasingly prolonged survival in metastatic colorectal cancer has paralleled the approval of new agents alone and in combination. Most recently, several new agents have sought approval in the heavily pretreated setting, after treatment with standard chemotherapies, alone and in combination, and with anti-vascular endothelial growth factor receptor and anti-epidermal growth factor receptor (for patients with RAS wild-type tumors). These agents have included the multitargeted tyrosine kinase inhibitor (TKI), regorafenib, and the novel antimetabolite combination, TAS-102. Both of these showed improvement in progression-free survival and overall survival compared with placebo controls and were approved in the United States and the rest of the world. Benefits of treatment and toxicities are discussed. Nintedanib, another multitargeted TKI, is already approved by the European Medicines Evaluation Agency for non-small cell lung cancer and has been studied in a similar phase III trial. Results are pending. The risks and benefits of each agent are discussed.
authors.affiliation: From the Yale Cancer Center and Yale School of Medicine, New Haven, CT.
authors.forename: Saurin
authors.initials: S
authors.lastname: Chokshi
authors.forename: Howard S
authors.initials: HS
authors.lastname: Hochster
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D006801:Humans; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011759:Pyrrolidines; D019233:Retreatment; D013941:Thymine; D016896:Treatment Outcome; D014271:Trifluridine / Q000494:pharmacology / Q000627:therapeutic use; D014498:Uracil / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D047428:Protein Kinase Inhibitors; D011759:Pyrrolidines; C000613803:trifluridine tipiracil drug combination; D014498:Uracil; D013941:Thymine; D014271:Trifluridine