Aapro, M., Karthaus, M., Schwartzberg, L., Bondarenko, I., Sarosiek, T., Oprean, C., . . . Rugo, H. (2017). NEPA, a fixed oral combination of netupitant and palonosetron, improves control of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of chemotherapy: Results of a randomized, double-blind, phase 3 trial versus oral palonosetron. Supportive Care in Cancer, 25, 1127–1135. 

To compare the efficacy and safety of netupitant plus palonosetron (NEPA) compared to palonosetron alone in preventing chemotherapy-induced nausea and vomiting (CINV)

Chemotherapy-naïve patients receiving anthracycline- or cyclophosphamide-based chemotherapy were randomized to receive a single dose of PO NEPA (300 mg netupitant plus 0.50 mg palonosetron) and 12 mg dexamethasone or a single dose of 0.5 mg PO palonosetron and 20 mg dexamethasone on day 1, cycle 1, of their chemotherapy. Delayed (25-120 hours post chemotherapy) CINV was evaluated as the primary end point.

• N = 1,455 (participated in a total of 5,969 chemotherapy cycle extension)   
• MEDIAN AGE = 54 years
• MALES: 2%, FEMALES: 98%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Solid tumor cancer, 98% with breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Aged older than 18 years; chemotherapy-naïve; anthracycline- or cyclophosphamide-based chemotherapy; European Cooperative Oncology Group (ECOG) score of 0, 1, or 2; not receiving prolonged chemotherapy from day 1-5; not receiving abdominal radiotherapy; no bone marrow transplantation; did not received any antiemetics 24 hours before chemotherapy and did not experience anticipatory nausea and vomiting

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Multinational

PHASE OF CARE: Active antitumor treatment

Double-blind, randomized

• Diary: Emesis episodes and rescue medications used from 0-120 hour each cycle
• Visual analog scale (VAS) for nausea from 0 (no nausea) to 100 (nausea as bad as it could be)
• Proportion of patients with complete response (0-120 hours)
• Review treatment emergent adverse effects, ECG, troponin levels

Participants who received NEPA and dexamethasone reported complete remission (no emesis or rescue antiemetics) significantly more than participants who received palonosetron and dexamethasone (p ≤ 0.001).

NEPA and dexamethasone may offer more control over CINV compared to palonosetron and dexamethasone.

• Measurement validity/reliability questionable
• Using VAS for nausea and vomiting

Combination antiemetic therapies have been shown to provide more relief from CINV compared to single agents. The results of this study demonstrated that NEPA given with dexamethasone did prevent CINV better than palonosetron and dexamethasone.