HPE Managing CINV pocket guide 2019 | Page 38

due to be treated with cisplatin- based HEC, Karthaus et al reported that, in the acute phase, the majority of patients (89.4% in the oral palonosetron group and 86.2% in the IV palonosetron group) achieved a CR. The non-inferiority of oral palonosetron compared with IV palonosetron was thus demonstrated, as assessed by the primary efficacy endpoint (CR in the acute phase) in both the full analysis set and per-protocol populations. All the planned sensitivity analyses supported the non-inferiority of oral palonosetron compared with IV palonosetron. The two treatment groups also showed comparable CR in the delayed (76.2% oral vs 74.8% IV) and overall phases (73.7 oral vs 70.2 IV), and the results of the secondary efficacy endpoints in all three phases were similar. Thus, the results of the secondary efficacy endpoints also support the demonstration of non-inferiority. 24 The safety of IV palonosetron has been demonstrated in several Phase III clinical trials. 20,25–27 Karthaus et al comment that their study further supports these findings as the safety profiles of oral palonosetron and IV palonosetron were comparable and raised no new concerns. 24 The use of orally administered antiemetics for prophylaxis of nausea and emesis in patients receiving HEC treatment, in particular, for the control of 38 | 2019 | hospitalpharmacyeurope.com nausea and vomiting on the first day of cisplatin treatment has been questioned. 28 The study by Karthaus et al clearly demonstrated the non- inferiority of oral palonosetron versus IV palonosetron administration when both are used with dexamethasone. 24 The use of oral palonosetron might be beneficial, as it would allow a more convenient prophylaxis, which is proven to be effective in controlling CINV caused by HEC. This may be of particular help for patients who receive treatment in an outpatient setting. A similar study of efficacy and safety assessing the non-inferiority of oral versus IV formulations of palonosetron has been performed also in the MEC setting. 29 Oral combination therapy might be another attractive option for some patients and there is some evidence that fixed combinations can encourage improved adherence compared with giving drugs separately. 30 Because their mechanisms of action target different neurotransmitter pathways involved in nausea and vomiting, combination therapy with a NK 1 RA and 5-HT 3 RA represents a rational therapeutic strategy. 31,32 For example, NEPA (an oral fixed combination of netupitant 300mg and palonosetron 0.5mg) given on day one of each chemotherapy cycle together with dexamethasone, was effective and