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

Matti Aapro, H. Rugo, G. Rossi, G. Rizzi, M. E. Borroni, I. Bondarenko, T. Sarosiek, C. Oprean, S. Cardona-Huerta, V. Lorusso, M. Karthaus, Lee Schwartzberg, S. Grunberg

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Abstract

Background: 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. Patients and methods: This multinational, randomized, double-blind, parallel group phase III study (NCT01339260) in 1455 chemotherapy-naïve 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. Results: The percentage of patients with CR during the delayed phasewas 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. NEPAwas 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). NEPAwas well tolerated with a similar safety profile as PALO. Conclusions: 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.

Original languageEnglish (US)
Article numbermdu101
Pages (from-to)1328-1333
Number of pages6
JournalAnnals of Oncology
Volume25
Issue number7
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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Nausea
Vomiting
Safety
Drug Therapy
Dexamethasone
Antiemetics
Guidelines
Serotonin 5-HT3 Receptor Antagonists
Receptors, Serotonin, 5-HT3
Anthracyclines
Drug Combinations
netupitant
palonosetron
Cyclophosphamide
Observation

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

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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. / Aapro, Matti; Rugo, H.; Rossi, G.; Rizzi, G.; Borroni, M. E.; Bondarenko, I.; Sarosiek, T.; Oprean, C.; Cardona-Huerta, S.; Lorusso, V.; Karthaus, M.; Schwartzberg, Lee; Grunberg, S.

In: Annals of Oncology, Vol. 25, No. 7, mdu101, 01.01.2014, p. 1328-1333.

Research output: Contribution to journalArticle

Aapro, Matti ; Rugo, H. ; Rossi, G. ; Rizzi, G. ; Borroni, M. E. ; Bondarenko, I. ; Sarosiek, T. ; Oprean, C. ; Cardona-Huerta, S. ; Lorusso, V. ; Karthaus, M. ; Schwartzberg, Lee ; Grunberg, S. / 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. In: Annals of Oncology. 2014 ; Vol. 25, No. 7. pp. 1328-1333.
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abstract = "Background: 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. Patients and methods: This multinational, randomized, double-blind, parallel group phase III study (NCT01339260) in 1455 chemotherapy-na{\"i}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. Results: The percentage of patients with CR during the delayed phasewas 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. NEPAwas 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). NEPAwas well tolerated with a similar safety profile as PALO. Conclusions: 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.",
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T1 - 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

AU - Aapro, Matti

AU - Rugo, H.

AU - Rossi, G.

AU - Rizzi, G.

AU - Borroni, M. E.

AU - Bondarenko, I.

AU - Sarosiek, T.

AU - Oprean, C.

AU - Cardona-Huerta, S.

AU - Lorusso, V.

AU - Karthaus, M.

AU - Schwartzberg, Lee

AU - Grunberg, S.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background: 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. Patients and methods: This multinational, randomized, double-blind, parallel group phase III study (NCT01339260) in 1455 chemotherapy-naïve 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. Results: The percentage of patients with CR during the delayed phasewas 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. NEPAwas 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). NEPAwas well tolerated with a similar safety profile as PALO. Conclusions: 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.

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