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

Abstract

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.

Abstract

Background

Antiemetic guidelines recommend co-administration of agents that target multiple molecular pathways involved in emesis to maximize prevention and control of chemotherapy-induced nausea and vomiting (CINV). NEPA is a new oral fixed-dose combination of 300 mg netupitant, a highly selective NK ₁ receptor antagonist (RA) and 0.50 mg palonosetron (PALO), a pharmacologically and clinically distinct 5-HT ₃ RA, which targets dual antiemetic pathways.

Patients and methods

This multinational, randomized, double-blind, parallel group phase III study (NCT01339260) in 1455 chemotherapy-naïve patients receiving moderately emetogenic (anthracycline–cyclophosphamide) chemotherapy evaluated the efficacy and safety of a single oral dose of NEPA versus a single oral dose (0.50 mg) of PALO. All patients also received oral dexamethasone (DEX) on day 1 only (12 mg in the NEPA arm and 20 mg in the PALO arm). The primary efficacy end point was complete response (CR: no emesis, no rescue medication) during the delayed (25–120 h) phase in cycle 1.

Results

The percentage of patients with CR during the delayed phase was significantly higher in the NEPA group compared with the PALO group (76.9% versus 69.5%; P = 0.001), as were the percentages in the overall (0–120 h) (74.3% versus 66.6%; P = 0.001) and acute (0–24 h) (88.4% versus 85.0%; P = 0.047) phases. NEPA was also superior to PALO during the delayed and overall phases for all secondary efficacy end points of no emesis, no significant nausea and complete protection (CR plus no significant nausea). NEPA was well tolerated with a similar safety profile as PALO.

Conclusions

NEPA plus a single dose of DEX was superior to PALO plus DEX in preventing CINV following moderately emetogenic chemotherapy in acute, delayed and overall phases of observation. As a fixed-dose antiemetic drug combination, NEPA along with a single dose of DEX on day 1 offers guideline-based prophylaxis with a convenient, single-day treatment.