Abstract P5-15-01: Evaluation of sustained antiemetic efficacy over repeated cycles of anthracycline-cyclophosphamide (AC)-based chemotherapy: A phase 3 study of NEPA, a fixed-dose combination of netupitant and palonosetron for prevention of chemotherapy-induced nausea and
Authors: Aapro Matti , Rugo Hope , Rizzi Giada 
Published: May 2015

Background: International antiemetic guidelines recommend co-administration of an NK1 receptor antagonist (RA) and a 5-HT3 RA in breast cancer (BC) patients receiving anthracycline cyclophosphamide (AC) chemotherapy as this population is at increased risk of developing CINV. NEPA, a novel, oral fixed-dose combination of a new NK1 receptor antagonist (RA), netupitant (NETU 300 mg), and the 5-HT3 RA, palonosetron (PALO 0.50 mg), was previously reported to be superior to oral PALO after a single cycle (Aapro et al, Annals of Oncology 2014) and multiple cycles (Aapro et al, ASCO 2014) of chemotherapy. This posthoc analysis evaluates sustained efficacy over multiple cycles when censoring patients who experienced CINV in the previous cycle.

Methods: This was a multinational, randomized, double-blind, parallel group study evaluating the efficacy/safety of single oral doses of NEPA versus oral PALO in chemotherapy-naïve patients receiving multiple cycles of anthracycline-based chemotherapy. All patients also received oral dexamethasone (DEX) 12 mg (NEPA) or 20 mg (PALO), only on Day 1. Overall (0-120 h) complete response (CR: no emesis, no rescue medication) was the efficacy endpoint evaluated. The analysis of sustained CR evaluates the probability that patients would remain complete responders over 4 cycles by censoring continuing patients who failed to have a CR in the prior cycle. A Kaplan Meier method and log-rank test comparing NEPA with oral PALO were utilized.

Results: 1455 patients were randomized; 1286 participated in the multiple cycle extension after cycle 1. Treatment groups were comparable with 98% females and 97% with BC; the mean age was 54. The percentage of patients who experienced a CR in cycle 1 and who sustained a CR over cycles 2-4 was greater for NEPA than for oral PALO (p &lt;0.0001, log rank test). The table shows the percent of patients with continuing CR over time; N = the number of patients at risk.

Time since first chemotherapyNEPA + DEXOral PALO + DEXCycle 174.3% (N = 724)66.6% (N = 725)Cycle 268.5% (N = 485)57.1% (N = 434)Cycle 365.7% (N = 423)52.7% (N = 348)Cycle 463.6% (N = 375)50.6% (N = 300)

Conclusions: This multiple cycle analysis indicates that NEPA, a novel, fixed-dose antiemetic combination, more effectively demonstrates sustained control of CINV over multiple cycles than oral PALO. As females with breast cancer represent a particularly challenging population in terms of emesis control, it is especially crucial that antiemetic recommendations are followed to allow these patients to maintain their quality of life and continue their treatment plan over multiple cycles of chemotherapy. NEPA offers effective guideline-recommended prophylaxis in a convenient single dose.

Citation Format: Matti Aapro, Hope Rugo, Giada Rizzi. Evaluation of sustained antiemetic efficacy over repeated cycles of anthracycline-cyclophosphamide (AC)-based chemotherapy: A phase 3 study of NEPA, a fixed-dose combination of netupitant and palonosetron for prevention of chemotherapy-induced nausea and [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-15-01.