Aapro, M., Rugo, H., Rossi, G., Rizzi, G., Borroni, M.E., Bondarenko, I., ... Grunberg, S. (2014). 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. Annals of Oncology, 25, 1328–1333. 

To evaluate the safety and efficacy of NEPA (a combination of netupitant plus palonosetron) compared to palonosetron (PALO) alone

During cycle 1 of moderately emetogenic chemotherapy, patients received either a single dose of NEPA (a combination of 300 mg netupitant and 0.50 mg palonosetron) plus 12 mg dexamethasone, or a single dose of 0.50 mg palonosetron (PALO) plus 20 mg dexamethasone. Patients were randomized and stratified by region. Matching placebos were used for blinding in all groups. Metoclopramide tablets were provided for breakthrough, though treating physicians could select another medication. Data were collected daily on days 1–6 after chemotherapy (0–120 hours).

• N = 1449  
• MEDIAN AGE = 54 years
• MALES: 1.9%, FEMALES: 98.1%
• KEY DISEASE CHARACTERISTICS: Primarily breast cancer (97.5%)
• OTHER KEY SAMPLE CHARACTERISTICS: Chemotherapy-naïve patients receiving moderately emetogenic chemotherapy with an ECOG performance status ≤ 2

• SITE: Multi-site    
• SETTING TYPE: Not specified    
• LOCATION: Multinational

PHASE OF CARE: Active antitumor treatment

Phase 3 trial, multicenter, randomized, double-blind, double-dummy, parallel group design

• Patient diary (timing and duration of emetic episode, severity of nausea, rescue medications needed)
• Visual analog scale (VAS) of pain
• The Functional Living Index-Emesis (FLIE) 
• Primary endpoint: Complete response (CR)

A significant number of patients in the NEPA group achieved CR when compared to patients in the PALO group overall (p = 0.001), in the delayed phase of treatment (p = 0.001), and during the acute phase of treatment (p = 0.047).

NEPA, the combination of netupitant and palonosetron, was demonstrated to be safe and more effective than palonosetron alone in producing CR during the acute, delayed, and overall phases of treatment in patients receiving cycle 1 of moderately emetogenic therapy.

• Risk of bias (sample characteristics)
• Other limitations/explanation: More than 98% of the participants in the study were women. Of those, more than 97% were diagnosed with breast cancer.

Chemotherapy-induced nausea and vomiting (CINV) guidelines recommend antiemetic therapies targeting multiple pathways involved in emesis. NEPA, the novel combination of netupitant and palonosetron, uses an NK1 receptor antagonist and a 5-HT3 receptor antagonist to maximize CINV control. NEPA was shown to be more effective than palonosetron alone in producing CR during the acute, delayed, and overall phases of cycle 1 of moderately emetogenic therapy. The majority of this sample, however, were women diagnosed with breast cancer. The findings may not be generalizable to males or to other types of cancer.