Abstract P1-10-06: Nausea control and quality-of-life benefit with NEPA, the first combination antiemetic agent, in patients with breast cancer receiving anthracycline/cyclophosphamide (AC) chemotherapy
Authors: Rugo HS , Aapro M , Rizzi G 
Published: May 2016

Background: Patients (pts) with breast cancer (BC) are at high risk for developing chemotherapy-induced nausea and vomiting (CINV) due to the emetogenicity of chemotherapy (often AC-based) and predisposing risk factors including young age and female gender. For pts receiving AC, antiemetic guidelines recommend prophylactic administration of an NK1 receptor antagonist (RA), a 5-HT3 RA, and dexamethasone (DEX). NEPA is the first fixed combination agent approved in oncology; comprised of a highly selective NK1 receptor antagonist (RA), netupitant (300 mg), and the pharmacologically/clinically distinct 5-HT3 RA, palonosetron (PALO 0.50 mg). NEPA has shown superior complete response (no emesis/no rescue use) rates compared with oral PALO in a Phase 3 trial in pts receiving AC (Aapro, Ann Oncol 2014) and in that study's BC subset. Despite progress in prevention of vomiting, nausea control remains suboptimal, particularly in the delayed phase (days 2-5), and debate exists whether NK1 RAs improve nausea control. The objective of this post-hoc analysis was to evaluate whether NEPA showed nausea and associated quality-of-life (QOL) benefits in the subset of patients with BC in this trial.

Methods: The subset of chemotherapy-naïve BC pts from this multinational, randomized, double-blind Phase 3 study were included in this analysis. Patients received either a single dose of NEPA or oral PALO prior to AC along with oral DEX 12 mg (NEPA) or 20 mg (PALO). No significant nausea (NSN: max &lt;25 mm on 100 mm visual analog scale) rates in the acute (0-24h), delayed (25-120h) and overall (0-120h) phases following chemotherapy during cycles 1-4 were calculated. QOL was assessed by the Functional Living Index—Emesis (FLIE) during cycle 1 overall phase; the percentage of pts with "no impact on daily life" (NIDL) was calculated. Comparisons between groups were performed using a Cochran-Maentel-Haenszel test.

Results: 1412 patients with BC were included for a total of 5839 AC cycles. NSN rates were similar for both groups in the acute phase, superior for NEPA during cycles 1, 2 and 4 in the delayed phase, and superior for NEPA during cycles 1-4 in the overall phase.

Overall NSN (0-120h)NEPA + DEXOral PALO + DEXP ValueCycle 174.2% (N = 708)68.5% (N = 704)0.016Cycle 277.0% (N = 621)71.1% (N = 636)0.015Cycle 378.2% (N = 586)72.7% (N = 594)0.027Cycle 479.9% (N = 542)74.9% (N = 550)0.040

This corresponded with a significantly greater proportion of NEPA patients reporting NIDL compared with PALO due to nausea (71% vs 65%; p=0.007) in cycle 1.

Conclusions: While other NK1RAs have not consistently shown benefit in improving nausea control over 5-HT3RA + DEX, in this study NEPA significantly improved prevention of nausea over oral PALO in BC patients receiving AC. In addition, NEPA was superior to PALO in reducing the negative impact of nausea on patients' daily functioning. As the first fixed antiemetic drug combination, NEPA is highly effective and offers the convenience of a single dose administered with DEX on Day 1 only.

Citation Format: Rugo HS, Aapro M, Rizzi G. Nausea control and quality-of-life benefit with NEPA, the first combination antiemetic agent, in patients with breast cancer receiving anthracycline/cyclophosphamide (AC) chemotherapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-10-06.