A new two drug oral combination drug consisting of the investigational agent netupitant and palonosetron (Aloxi, Eisai), given with a dose of dexamethasone, is more effective than palonosetron plus dexamethasone in preventing chemotherapy-induced nausea and vomiting (CINV). Netupitant is a highly selective NK1 receptor antagonist and palonosetron is a 5-HT3 receptor antagonist. The new two drug regimen, abbreviated NEPA, is a fixed-dose drug combining netupitant and palonosetron. The randomized, double-blind Phase III trial was conducted at 177 sites in 15 countries. In one study arm, 725 patients were given a single oral dose of palonosetron (0.50 mg) plus dexamethasone (20 mg) on day 1 of chemotherapy. In the other group, 724 patients received netupitant (300 mg) and palonosetron (0.50 mg) plus dexamethasone (12 mg). The clinical trial evaluated efficacy in the acute (0- to 24-hour), delayed (25- to 120-hour) and overall (0- to 120-hour) time periods following chemotherapy.
Complete response (CR) was defined as no vomiting or retching, and no need for rescue medication. The NEPA cohort was superior to palonosetron alone during the delayed and overall periods (76.9% vs. 69.5% 25-120 hours post chemotherapy and 74.3% vs. 66.66 overall).A slight advantage to treatment with NEPA was also demonstrated in the acute period (88.4% vs. 85.0%).Incidence, type, frequency and intensity of study-related adverse events (AEs) were comparable in both treatment arms. Less than 2% of patients in both groups reported serious adverse events and common complaints were headache and constipation.
Aapro M, Rugo H, Rossi G. A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy. Ann Oncol 2014; 25: 1328-1333.