A randomized phase III 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)

• Verfasst von: Zhang, Li [VerfasserIn]
• Verfasst von: Jordan, Karin [VerfasserIn]
• Titel: A randomized phase III 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)
• Verf.angabe: L. Zhang, S. Lu, J. Feng, A. Dechaphunkul, J. Chang, D. Wang, S. Chessari, C. Lanzarotti, K. Jordan & M. Aapro
• Jahr: 2018
• Jahr des Originals: 2017
• Umfang: 7 S.
• Fussnoten: Published online 28 October 2017 ; Gesehen am 31.03.2020
• Titel Quelle: Enthalten in: Annals of oncology
• Ort Quelle: Amsterdam [u.a. : Elsevier, 1990
• Jahr Quelle: 2018
• Band/Heft Quelle: 29(2018), 2, Seite 452-458
• ISSN Quelle: 1569-8041
• DOI: doi:10.1093/annonc/mdx698
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1693614863

Abstract

<h2>ABSTRACT</h2><h3>Background</h3><p>Co-administration of multiple antiemetics that inhibit several molecular pathways involved in emesis is required to optimize chemotherapy-induced nausea and vomiting (CINV) control in patients receiving highly emetogenic chemotherapy (HEC). NEPA, a fixed combination of a highly selective NK₁ receptor antagonist, netupitant (300 mg), and the pharmacologically distinct 5-HT₃RA, palonosetron (PALO 0.50 mg), has shown superior CINV prevention compared with 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.</p><h3>Patients and methods</h3><p>This randomized, double-blind phase III 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).</p><h3>Results</h3><p>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% versus APR/GRAN 72.4%, 95% CI (−4.5%, 7.5%)]. No emesis [NEPA 75.0% versus APR/GRAN 74.0%, 95% CI (−4.8%, 6.9%)] and NSN rates [NEPA 75.7% versus 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% versus APR/GRAN 93.5%, 95% CI (0.2%, 6.1%)]. NEPA was well tolerated with a similar safety profile to APR/GRAN.</p><h3>Conclusions</h3><p>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.</p>