NEPA is an oral single, fixed-dose combination of netupitant, a new highly selective NK 1 RA and palonosetron (PALO), a pharmacologically/clinically distinct 5-HT 3 RA. It delivers antiemetic guideline-recommended prophylaxis by targeting two critical molecular pathways associated with chemotherapy-induced nausea/vomiting. This Phase III study demonstrated the superiority of NEPA compared with PALO.

This study was designed to determine the appropriate clinical dose of netupitant (NETU), a new NK 1 receptor antagonist (RA), to combine with the 5-HT 3 RA, palonosetron (PALO) in a fixed-dose antiemetic combination (NEPA). All NEPA doses provided superior prevention of chemotherapy-induced nausea and vomiting compared with PALO, with NEPA 300 (300mg NETU + 0.50 mg PALO) being the best dose studied.

In this multinational, phase III study, the safety and efficacy of NEPA, a convenient, fixed-dose antiemetic combination of netupitant, a highly selective NK 1 receptor antagonist (RA), and palonosetron, a distinct 5-HT 3 RA, were evaluated over multiple cycles of highly and moderately emetogenic chemotherapy. NEPA was shown to be safe, well tolerated and highly effective over 1961 chemotherapy cycles.

Intravenous NEPA was well-tolerated with a similar safety profile to oral NEPA in patients with various solid tumors receiving HEC.

PurposeAntiemetic guidelines recommend co-administration of targeted prophylactic medications inhibiting molecular pathways involved in emesis. NEPA is a fixed oral combination of a new NK1 receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3 RA. NEPA showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with oral PALO in a single chemotherapy cycle; maintenance of efficacy/safety over continuing cycles is the objective of this study.MethodsThis study is a multinational, double-blind study comparing a single oral dose of NEPA vs oral PALO in chemotherapy-naïve patients receiving anthracycline/cyclophosphamide-based chemotherapy along with dexamethasone 12 mg (NEPA) or 20 mg (PALO) on day 1. The primary efficacy endpoint was delayed (25–120 h) complete response (CR: no emesis, no rescue medication) in cycle 1. Sustained efficacy was evaluated during the multicycle extension by calculating the proportion of patients with overall (0–120 h) CR in cycles 2–4 and by assessing the probability of sustained CR over multiple cycles.ResultsOf 1455 patients randomized, 1286 (88 %) participated in the multiple-cycle extension for a total of 5969 cycles; 76 % completed ≥4 cycles. The proportion of patients with an overall CR was significantly greater for NEPA than oral PALO for cycles 1–4 (74.3 vs 66.6 %, 80.3 vs 66.7 %, 83.8 vs 70.3 %, and 83.8 vs 74.6 %, respectively; p ≤ 0.001 each cycle). The cumulative percentage of patients with a sustained CR over all 4 cycles was also greater for NEPA (p < 0.0001). NEPA was well tolerated over cycles.ConclusionsNEPA, a convenient, guideline-consistent, fixed antiemetic combination is effective and safe over multiple cycles of chemotherapy.