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)

Abstract

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.