NEPA, a fixed oral combination of netupitant and palonosetron, improves control of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of chemotherapy

results of a randomized, double-blind, phase 3 trial versus oral palonosetron

Matti Aapro, Meinolf Karthaus, Lee Schwartzberg, Igor Bondarenko, Tomasz Sarosiek, Cristina Oprean, Servando Cardona-Huerta, Vincent Hansen, Giorgia Rossi, Giada Rizzi, Maria Elisa Borroni, Hope Rugo

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Purpose: Antiemetic guidelines recommend co-administration of targeted prophylactic medications inhibiting molecular pathways involved in emesis. NEPA is a fixed oral combination of a new NK1 receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3 RA. NEPA showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with oral PALO in a single chemotherapy cycle; maintenance of efficacy/safety over continuing cycles is the objective of this study. Methods: This study is a multinational, double-blind study comparing a single oral dose of NEPA vs oral PALO in chemotherapy-naïve patients receiving anthracycline/cyclophosphamide-based chemotherapy along with dexamethasone 12 mg (NEPA) or 20 mg (PALO) on day 1. The primary efficacy endpoint was delayed (25–120 h) complete response (CR: no emesis, no rescue medication) in cycle 1. Sustained efficacy was evaluated during the multicycle extension by calculating the proportion of patients with overall (0–120 h) CR in cycles 2–4 and by assessing the probability of sustained CR over multiple cycles. Results: Of 1455 patients randomized, 1286 (88 %) participated in the multiple-cycle extension for a total of 5969 cycles; 76 % completed ≥4 cycles. The proportion of patients with an overall CR was significantly greater for NEPA than oral PALO for cycles 1–4 (74.3 vs 66.6 %, 80.3 vs 66.7 %, 83.8 vs 70.3 %, and 83.8 vs 74.6 %, respectively; p ≤ 0.001 each cycle). The cumulative percentage of patients with a sustained CR over all 4 cycles was also greater for NEPA (p < 0.0001). NEPA was well tolerated over cycles. Conclusions: NEPA, a convenient, guideline-consistent, fixed antiemetic combination is effective and safe over multiple cycles of chemotherapy.

Original languageEnglish (US)
Pages (from-to)1127-1135
Number of pages9
JournalSupportive Care in Cancer
Volume25
Issue number4
DOIs
StatePublished - Apr 1 2017

Fingerprint

Nausea
Vomiting
Drug Therapy
Antiemetics
Guidelines
Serotonin 5-HT3 Receptor Antagonists
Receptors, Serotonin, 5-HT3
Anthracyclines
Double-Blind Method
Cyclophosphamide
Dexamethasone
Maintenance
palonosetron
netupitant
Safety

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

NEPA, a fixed oral combination of netupitant and palonosetron, improves control of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of chemotherapy : results of a randomized, double-blind, phase 3 trial versus oral palonosetron. / Aapro, Matti; Karthaus, Meinolf; Schwartzberg, Lee; Bondarenko, Igor; Sarosiek, Tomasz; Oprean, Cristina; Cardona-Huerta, Servando; Hansen, Vincent; Rossi, Giorgia; Rizzi, Giada; Borroni, Maria Elisa; Rugo, Hope.

In: Supportive Care in Cancer, Vol. 25, No. 4, 01.04.2017, p. 1127-1135.

Research output: Contribution to journalArticle

Aapro, Matti ; Karthaus, Meinolf ; Schwartzberg, Lee ; Bondarenko, Igor ; Sarosiek, Tomasz ; Oprean, Cristina ; Cardona-Huerta, Servando ; Hansen, Vincent ; Rossi, Giorgia ; Rizzi, Giada ; Borroni, Maria Elisa ; Rugo, Hope. / NEPA, a fixed oral combination of netupitant and palonosetron, improves control of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of chemotherapy : results of a randomized, double-blind, phase 3 trial versus oral palonosetron. In: Supportive Care in Cancer. 2017 ; Vol. 25, No. 4. pp. 1127-1135.
@article{55e314bf0411472a9255b3589a08d380,
title = "NEPA, a fixed oral combination of netupitant and palonosetron, improves control of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of chemotherapy: results of a randomized, double-blind, phase 3 trial versus oral palonosetron",
abstract = "Purpose: Antiemetic guidelines recommend co-administration of targeted prophylactic medications inhibiting molecular pathways involved in emesis. NEPA is a fixed oral combination of a new NK1 receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3 RA. NEPA showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with oral PALO in a single chemotherapy cycle; maintenance of efficacy/safety over continuing cycles is the objective of this study. Methods: This study is a multinational, double-blind study comparing a single oral dose of NEPA vs oral PALO in chemotherapy-na{\"i}ve patients receiving anthracycline/cyclophosphamide-based chemotherapy along with dexamethasone 12 mg (NEPA) or 20 mg (PALO) on day 1. The primary efficacy endpoint was delayed (25–120 h) complete response (CR: no emesis, no rescue medication) in cycle 1. Sustained efficacy was evaluated during the multicycle extension by calculating the proportion of patients with overall (0–120 h) CR in cycles 2–4 and by assessing the probability of sustained CR over multiple cycles. Results: Of 1455 patients randomized, 1286 (88 {\%}) participated in the multiple-cycle extension for a total of 5969 cycles; 76 {\%} completed ≥4 cycles. The proportion of patients with an overall CR was significantly greater for NEPA than oral PALO for cycles 1–4 (74.3 vs 66.6 {\%}, 80.3 vs 66.7 {\%}, 83.8 vs 70.3 {\%}, and 83.8 vs 74.6 {\%}, respectively; p ≤ 0.001 each cycle). The cumulative percentage of patients with a sustained CR over all 4 cycles was also greater for NEPA (p < 0.0001). NEPA was well tolerated over cycles. Conclusions: NEPA, a convenient, guideline-consistent, fixed antiemetic combination is effective and safe over multiple cycles of chemotherapy.",
author = "Matti Aapro and Meinolf Karthaus and Lee Schwartzberg and Igor Bondarenko and Tomasz Sarosiek and Cristina Oprean and Servando Cardona-Huerta and Vincent Hansen and Giorgia Rossi and Giada Rizzi and Borroni, {Maria Elisa} and Hope Rugo",
year = "2017",
month = "4",
day = "1",
doi = "10.1007/s00520-016-3502-x",
language = "English (US)",
volume = "25",
pages = "1127--1135",
journal = "Supportive Care in Cancer",
issn = "0941-4355",
publisher = "Springer Verlag",
number = "4",

}

TY - JOUR

T1 - NEPA, a fixed oral combination of netupitant and palonosetron, improves control of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of chemotherapy

T2 - results of a randomized, double-blind, phase 3 trial versus oral palonosetron

AU - Aapro, Matti

AU - Karthaus, Meinolf

AU - Schwartzberg, Lee

AU - Bondarenko, Igor

AU - Sarosiek, Tomasz

AU - Oprean, Cristina

AU - Cardona-Huerta, Servando

AU - Hansen, Vincent

AU - Rossi, Giorgia

AU - Rizzi, Giada

AU - Borroni, Maria Elisa

AU - Rugo, Hope

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Purpose: Antiemetic guidelines recommend co-administration of targeted prophylactic medications inhibiting molecular pathways involved in emesis. NEPA is a fixed oral combination of a new NK1 receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3 RA. NEPA showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with oral PALO in a single chemotherapy cycle; maintenance of efficacy/safety over continuing cycles is the objective of this study. Methods: This study is a multinational, double-blind study comparing a single oral dose of NEPA vs oral PALO in chemotherapy-naïve patients receiving anthracycline/cyclophosphamide-based chemotherapy along with dexamethasone 12 mg (NEPA) or 20 mg (PALO) on day 1. The primary efficacy endpoint was delayed (25–120 h) complete response (CR: no emesis, no rescue medication) in cycle 1. Sustained efficacy was evaluated during the multicycle extension by calculating the proportion of patients with overall (0–120 h) CR in cycles 2–4 and by assessing the probability of sustained CR over multiple cycles. Results: Of 1455 patients randomized, 1286 (88 %) participated in the multiple-cycle extension for a total of 5969 cycles; 76 % completed ≥4 cycles. The proportion of patients with an overall CR was significantly greater for NEPA than oral PALO for cycles 1–4 (74.3 vs 66.6 %, 80.3 vs 66.7 %, 83.8 vs 70.3 %, and 83.8 vs 74.6 %, respectively; p ≤ 0.001 each cycle). The cumulative percentage of patients with a sustained CR over all 4 cycles was also greater for NEPA (p < 0.0001). NEPA was well tolerated over cycles. Conclusions: NEPA, a convenient, guideline-consistent, fixed antiemetic combination is effective and safe over multiple cycles of chemotherapy.

AB - Purpose: Antiemetic guidelines recommend co-administration of targeted prophylactic medications inhibiting molecular pathways involved in emesis. NEPA is a fixed oral combination of a new NK1 receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3 RA. NEPA showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with oral PALO in a single chemotherapy cycle; maintenance of efficacy/safety over continuing cycles is the objective of this study. Methods: This study is a multinational, double-blind study comparing a single oral dose of NEPA vs oral PALO in chemotherapy-naïve patients receiving anthracycline/cyclophosphamide-based chemotherapy along with dexamethasone 12 mg (NEPA) or 20 mg (PALO) on day 1. The primary efficacy endpoint was delayed (25–120 h) complete response (CR: no emesis, no rescue medication) in cycle 1. Sustained efficacy was evaluated during the multicycle extension by calculating the proportion of patients with overall (0–120 h) CR in cycles 2–4 and by assessing the probability of sustained CR over multiple cycles. Results: Of 1455 patients randomized, 1286 (88 %) participated in the multiple-cycle extension for a total of 5969 cycles; 76 % completed ≥4 cycles. The proportion of patients with an overall CR was significantly greater for NEPA than oral PALO for cycles 1–4 (74.3 vs 66.6 %, 80.3 vs 66.7 %, 83.8 vs 70.3 %, and 83.8 vs 74.6 %, respectively; p ≤ 0.001 each cycle). The cumulative percentage of patients with a sustained CR over all 4 cycles was also greater for NEPA (p < 0.0001). NEPA was well tolerated over cycles. Conclusions: NEPA, a convenient, guideline-consistent, fixed antiemetic combination is effective and safe over multiple cycles of chemotherapy.

UR - http://www.scopus.com/inward/record.url?scp=84996798812&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84996798812&partnerID=8YFLogxK

U2 - 10.1007/s00520-016-3502-x

DO - 10.1007/s00520-016-3502-x

M3 - Article

VL - 25

SP - 1127

EP - 1135

JO - Supportive Care in Cancer

JF - Supportive Care in Cancer

SN - 0941-4355

IS - 4

ER -