A randomized Phase 3 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
Ces deux études évaluent l'efficacité et la toxicité d'une combinaison orale de netupitant et de palonosétron pour prévenir les nausées et vomissements induits par une chimiothérapie chez des patients atteints de cancer
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, that targets dual antiemetic pathways.
Patients and Methods This multinational, randomized, double-blind, parallel group Phase 3 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 endpoint was complete response (CR: no emesis, no rescue medication) during the delayed (25-120 hr) phase in cycle 1.
Results The percentage of patients with CR during the delayed phase was significantly higher in the NEPA group compared with the PALO group (76.9% vs. 69.5%; P=0.001), as were the percentages in the overall (0-120 hr) (74.3% vs. 66.6%; P=0.001) and acute (0-24 hr) (88.4% vs. 85.0; P=0.047) phases. NEPA was also superior to PALO during the delayed and overall phases for all secondary efficacy endpoints 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.
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 dexamethasone on day 1 offers guideline-based prophylaxis with a convenient, single-day treatment.
Annals of Oncology , résumé, 2014