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Clinical Trial
. 2014 Jul;25(7):1328-1333.
doi: 10.1093/annonc/mdu101. Epub 2014 Mar 5.

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

M Aapro  1 , H Rugo  2 , G Rossi  3 , G Rizzi  3 , M E Borroni  3 , I Bondarenko  4 , T Sarosiek  5 , C Oprean  6 , S Cardona-Huerta  7 , V Lorusso  8 , M Karthaus  9 , L Schwartzberg  10 , S Grunberg  11
Affiliations
Clinical Trial

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

M Aapro et al. Ann Oncol. 2014 Jul.

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 NK1 receptor antagonist (RA) and 0.50 mg palonosetron (PALO), a pharmacologically and clinically distinct 5-HT3 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.

Keywords: CINV; NEPA; moderately emetogenic; netupitant; neurokinin-1 receptor antagonist; palonosetron.

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Figures

Figure 1.
Figure 1.
Consort diagram of the disposition of patients.
Figure 2.
Figure 2.
Complete response (no emesis, no rescue medication).
Figure 3.
Figure 3.
Proportion of patients with no impact on daily living (NIDL) based on Functional Living Index-Emesis (FLIE): Overall 0–120 h.
See this image and copyright information in PMC

Comment in

References

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