A Randomized Phase 3 Study Evaluating the Efficacy of Single-dose NEPA, a Fixed Antiemetic Combination of Netupitant and Palonosetron, Versus an Aprepitant Regimen for Prevention of Chemotherapy-induced Nausea and Vomiting (CINV) in Patients Receiving Highly Emetogenic Chemotherapy (HEC)
Mené en Asie sur 828 patients atteints de cancer, cet essai de phase III compare l'efficacité d'un traitement combinant nétupitant et palonosétron et d'un traitement combinant aprépitant et granisétron pour prévenir les nausées et vomisements induits par une chimiothérapie hautement émétisante
Background : Co-administration of multiple antiemetics that inhibit several molecular pathways involved in emesis is required to optimize CINV control in patients receiving highly emetogenic chemotherapy (HEC). NEPA, a fixed combination of a highly selective NK1 receptor antagonist (RA), netupitant (300 mg), and the pharmacologically distinct 5-HT3RA, palonosetron (PALO 0.50 mg), has shown superior CINV prevention compared to PALO in cisplatin and anthracycline/cyclophosphamide-based settings. This study is the first head-to-head comparison of NEPA versus an aprepitant (APR)/granisetron (GRAN) regimen. Patients and methods : This randomized, double-blind Phase 3 study conducted in Asia was designed with the primary objective to demonstrate non-inferiority of a single oral dose of NEPA compared with a 3-day oral APR/GRAN regimen in chemotherapy-naïve patients receiving cisplatin-based HEC. All patients also received oral dexamethasone (DEX) on days 1-4. The primary efficacy endpoint was complete response (CR: no emesis/no rescue medication) during the overall (0-120 h) phase. Non-inferiority was defined as a lower 95% CI greater than the non-inferiority margin set at -10%. Secondary efficacy endpoints included no emesis, no rescue medication, and no significant nausea (NSN). Results : Treatment groups were comparable for the 828 patients analyzed: predominantly male (71%); mean age 54.5 years; ECOG 0-1 (98%); lung cancer (58%). NEPA demonstrated non-inferiority to APR/GRAN for overall CR [NEPA 73.8% vs APR/GRAN 72.4%, 95%CI (-4.5%, 7.5%)]. No emesis [NEPA 75.0% vs APR/GRAN 74.0%, 95%CI (-4.8%, 6.9%)] and NSN rates [NEPA 75.7% vs APR/GRAN 70.4%, 95%CI (-0.6%, 11.4%)] were similar between groups, but significantly more NEPA patients did not take rescue medication [NEPA 96.6% vs APR/GRAN 93.5%, 95%CI (0.2%, 6.1%)]. NEPA was well tolerated with a similar safety profile to APR/GRAN. Conclusions : In this first study comparing NK1RA regimens and DEX, NEPA administered only on day 1 was non-inferior to a 3-day oral APR/GRAN regimen in preventing CINV associated with HEC.
Annals of Oncology 2017