A recent phase 3 trial has demonstrated that NEPA (Helsinn Healthcare, SA), an oral fixed-dose combination of netupitant, a new, highly selective neurokinin 1 (NK1) receptor antagonist, and palonosetron, a 5-HT3 receptor antagonist, is superior to palonosetron alone for the prevention of chemotherapy-induced nausea and vomiting (CINV).1

The trial included 1,450 patients from 15 countries who were chemotherapy-naïve and undergoing a first course of an anthracycline/cyclophosphamide chemotherapy regimen. Patients were randomly assigned to receive NEPA (netupitant 300 mg plus palonosetron 0.50 mg) plus 12 mg dexamethasone or palonosetron 0.50 mg plus 20 mg dexamethasone on day 1 of chemotherapy.

Patients used diaries to report the timing and duration of vomiting, the severity of nausea, and the use of rescue medication, and completed the Functional Living Index-Emesis questionnaire to report the quality-of-life effect of CINV.

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Improvement During All Phases

Complete response, defined as no vomiting and no use of rescue medication, was reported during the delayed phase (24 to 120 hours after the start of chemotherapy) by 76.9% of patients taking NEPA plus dexamethasone and 69.5% of patients taking palonosetron plus dexamethasone (P=0.001).

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The proportion of patients reporting complete response between 0 and 24 hours after the start of chemotherapy and, overall, were also significantly higher in the NEPA group (88.4% vs 85.0%; P=0.047, and 74.3% vs 66.6%; P=0.001, respectively).

During the delayed phase and, overall, NEPA was also more effective than palonosetron in preventing significant nausea.

Similar Safety Profiles

Treatment-related adverse events (TEAEs) were reported by 8.1% of patients in the NEPA group and 7.2%% in the palonosetron group. Serious AEs were uncommon, occurring in fewer than 2% of patients in each group, and no serious TEAEs were reported. The most common TEAEs were headache and constipation. Two patients in the palonosetron group and no patients in the NEPA group discontinued study medication due to a TEAE.

A significantly greater proportion of patients given NEPA reported that nausea and vomiting had no significant effect on daily life.

In addition to providing a long duration of inhibition of 5-HT3 receptor function, palonosetron inhibits crosstalk between the 5-HT3 and NK1 receptors. The combination of palonosetron and netupitant has been shown previously to have synergistic effects.2

It is notable that NEPA provided superior prophylaxis against nausea and vomiting during the delayed phase, a significant unmet need for many patients.

Current clinical guidelines recommend the use of a 5-HT3 receptor antagonist and dexamethasone when administering moderately emetogenic chemotherapy and a 5-HT3 receptor antagonist, dexamethasone, and a NK1 receptor antagonist when administering highly emetogenic chemotherapy.3 However, adherence to guidelines is poor—as many as 89% of patients receiving highly emetogenic chemotherapy do not receive recommended prophylaxis.4

As a single oral product combining agents from two guideline-recommended drug classes, NEPA may help improve adherence to recommendations for prevention of CINV.


  1. Aapro-Piacentini M, Rugo H, Rossi G, et al. A randomized phase 3 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. Ann Oncol. 2014 March 5 [Epub ahead of print].
  2. Stathis M, Pietra C, Rojas C, Slusher BS. Inhibition of substance P-mediated responses in NG108-15 cells by netupitant and palonosetron exhibit synergistic effects. Eur J Pharmacol. 2012;689(1-3):25-30.
  3. Roila F, Herrstedt J, Aapro M, et al. Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol. 2010;21(5):232-243.
  4. Burmeister H, Aebi S, Studer C, et al. Adherence to ESMO clinical recommendations for prophylaxis of chemotherapy-induced nausea and vomiting. Support Care Cancer. 2012;20(1):232-243.