Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting

To examine pharmacologic and clinical characteristics of neurokinin 1 (NK₁)-receptor antagonists (RAs) for preventing chemotherapy-induced nausea and vomiting (CINV) following highly or moderately emetogenic chemotherapy, a literature search was performed for clinical studies in patients at risk of CINV with any approved NK₁ RAs in the title or abstract: aprepitant (capsules or oral suspension), HTX019 (intravenous [IV] aprepitant), fosaprepitant (IV aprepitant prodrug), rolapitant (tablets or IV), and fixed-dose tablets combining netupitant or fosnetupi-tant (IV netupitant prodrug) with the 5-hydroxytryptamine type 3 (5HT₃) RA palonosetron (oral or IV). All NK₁ RAs are effective, but exhibit important differences in efficacy against acute and delayed CINV. The magnitude of benefit of NK₁-RA-containing three-drug vs two-drug regimens is greater for delayed vs acute CINV. Oral rolapitant has the longest half-life of available NK₁ RAs, but as a consequence should not be administered more frequently than every 2 weeks. In general, NK₁ RAs are well tolerated; however, IV rolapitant was recently removed from US distribution, due to hypersensitivity and anaphylaxis, and IV fosaprepitant is associated with infusion-site reactions and hypersensitivity presumed related to its polysorbate 80 excipient. Also, available NK₁ RAs have potential drug-drug interactions. Adding an NK₁ RA to 5HT₃ RA and dexamethasone significantly improves CINV control vs the two-drug regimen. Newer NK₁ RAs offer more formulation options, higher acute-phase plasma levels, or improved tolerability, and increase clinicians' opportunities to maximize benefits of this important class of antiemetics.