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2014 ; 25
(7
): 1340-1346
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gab.com Text
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English Wikipedia
Efficacy and safety of NEPA, an oral combination of netupitant and palonosetron,
for prevention of chemotherapy-induced nausea and vomiting following highly
emetogenic chemotherapy: a randomized dose-ranging pivotal study
#MMPMID24608196
Hesketh PJ
; Rossi G
; Rizzi G
; Palmas M
; Alyasova A
; Bondarenko I
; Lisyanskaya A
; Gralla RJ
Ann Oncol
2014[Jul]; 25
(7
): 1340-1346
PMID24608196
show ga
BACKGROUND: NEPA is a novel oral fixed-dose combination of netupitant (NETU), a
new highly selective neurokinin-1 (NK1) receptor antagonist (RA) and palonosetron
(PALO), a pharmacologically and clinically distinct 5-hydroxytryptamine type 3
(5-HT3) RA. This study was designed to determine the appropriate clinical dose of
NETU to combine with PALO for evaluation in the phase 3 NEPA program. PATIENTS
AND METHODS: This randomized, double-blind, parallel group study in 694
chemotherapy naïve patients undergoing cisplatin-based chemotherapy for solid
tumors compared three different oral doses of NETU (100, 200, and 300 mg) + PALO
0.50 mg with oral PALO 0.50 mg, all given on day 1. A standard 3-day aprepitant
(APR) + IV ondansetron (OND) 32 mg regimen was included as an exploratory arm.
All patients received oral dexamethasone on days 1-4. The primary efficacy
endpoint was complete response (CR: no emesis, no rescue medication) during the
overall (0-120 h) phase. RESULTS: All NEPA doses showed superior overall CR rates
compared with PALO (87.4%, 87.6%, and 89.6% for NEPA100, NEPA200, and NEPA300,
respectively versus 76.5% PALO; P < 0.050) with the highest NEPA300 dose studied
showing an incremental benefit over lower NEPA doses for all efficacy endpoints.
NEPA300 was significantly more effective than PALO and numerically better than
APR + OND for all secondary efficacy endpoints of no emesis, no significant
nausea, and complete protection (CR plus no significant nausea) rates during the
acute (0-24 h), delayed (25-120 h), and overall phases. Adverse events were
comparable across groups with no dose response. The percent of patients
developing electrocardiogram changes was also comparable. CONCLUSIONS: Each NEPA
dose provided superior prevention of chemotherapy-induced nausea and vomiting
(CINV) compared with PALO following highly emetogenic chemotherapy; however,
NEPA300 was the best dose studied, with an advantage over lower doses for all
efficacy endpoints. The combination of NETU and PALO was well tolerated with a
similar safety profile to PALO and APR + OND.