A randomized phase III 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

被引：210

作者：

Aapro, M. ^{[1
]}

Rugo, H. ^{[2
]}

Rossi, G. ^{[3
]}

Rizzi, G. ^{[3
]}

Borroni, M. E. ^{[3
]}

Bondarenko, I. ^{[4
]}

Sarosiek, T. ^{[5
]}

Oprean, C. ^{[6
]}

Cardona-Huerta, S. ^{[7
]}

Lorusso, V. ^{[8
]}

Karthaus, M. ^{[9
]}

Schwartzberg, L. ^{[10
]}

Grunberg, S. ^{[11
]}

机构：

[1] Clin Genolier, IMO, CH-1272 Genolier, Switzerland

[2] Univ Calif San Francisco, Comprehens Canc Ctr, San Francisco, CA 94143 USA

[3] Helsinn Healthcare, Corp Clin Dev, Stat & Data Management, Lugano, Switzerland

[4] Dnepropetrovsk Med Acad, Dept Oncol, Dnepropetrovsk, Ukraine

[5] Nzoz Magodent, Warsaw, Poland

[6] Oncomed SRL, Timisoara, Romania

[7] Univ Autonoma Nuevo Leon, Hosp Univ, Monterrey, Mexico

[8] Natl Canc Inst Giovanni Paolo II, Bari, Italy

[9] Staedt Klinikum Neuperlach & Harlaching, Dept Hematol Oncol & Palliat Med, Munich, Germany

[10] West Clin, Memphis, TN USA

[11] Fletcher Allen Hlth Care, Burlington, VT USA

来源：

ANNALS OF ONCOLOGY | 2014年 / 25卷 / 07期

关键词：

neurokinin-1 receptor antagonist; NEPA; netupitant; palonosetron; CINV; moderately emetogenic; ANTIEMETIC THERAPY; DEXAMETHASONE; TOLERABILITY;

D O I：

10.1093/annonc/mdu101

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Antiemetic guidelines recommend co-administration of agents that target multiple molecular pathways involved in emesis to maximize prevention and control of chemotherapy-induced nausea and vomiting (CINV). NEPA is a new oral fixed-dose combination of 300 mg netupitant, a highly selective NK1 receptor antagonist (RA) and 0.50 mg palonosetron (PALO), a pharmacologically and clinically distinct 5-HT3 RA, which targets dual antiemetic pathways. This multinational, randomized, double-blind, parallel group phase III study (NCT01339260) in 1455 chemotherapy-na < ve patients receiving moderately emetogenic (anthracycline-cyclophosphamide) chemotherapy evaluated the efficacy and safety of a single oral dose of NEPA versus a single oral dose (0.50 mg) of PALO. All patients also received oral dexamethasone (DEX) on day 1 only (12 mg in the NEPA arm and 20 mg in the PALO arm). The primary efficacy end point was complete response (CR: no emesis, no rescue medication) during the delayed (25-120 h) phase in cycle 1. The percentage of patients with CR during the delayed phase was significantly higher in the NEPA group compared with the PALO group (76.9% versus 69.5%; P = 0.001), as were the percentages in the overall (0-120 h) (74.3% versus 66.6%; P = 0.001) and acute (0-24 h) (88.4% versus 85.0%; P = 0.047) phases. NEPA was also superior to PALO during the delayed and overall phases for all secondary efficacy end points of no emesis, no significant nausea and complete protection (CR plus no significant nausea). NEPA was well tolerated with a similar safety profile as PALO. NEPA plus a single dose of DEX was superior to PALO plus DEX in preventing CINV following moderately emetogenic chemotherapy in acute, delayed and overall phases of observation. As a fixed-dose antiemetic drug combination, NEPA along with a single dose of DEX on day 1 offers guideline-based prophylaxis with a convenient, single-day treatment.

引用

页码：1328 / 1333

页数：6

共 13 条

[1]

The effect of guideline-consistent antiemetic therapy on chemotherapy-induced nausea and vomiting (CINV): the Pan European Emesis Registry (PEER) [J].