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
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 : NEPA is a novel oral fixed-dose combination of netupitant (NETU), a new highly selective NK1 receptor antagonist (RA) and palonosetron (PALO), a pharmacologically and clinically distinct 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 chemotherapynaïve patients undergoing cisplatin-based chemotherapy for solid tumors compared 3 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 hr) phase.
Results : All NEPA doses showed superior overall CR rates compared with PALO (87.4%, 87.6%, 89.6% for NEPA100, NEPA200, and NEPA300, respectively vs 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 hr), delayed (25-120 hr) and overall phases.Adverse events were comparable across groups with no dose-response. The percent of patients developing ECG changes was also comparable.
Conclusions : Each NEPA dose provided superior prevention of 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.
Annals of Oncology , résumé, 2014