Suboptimal CINV prevention can negatively impact patients’ (pts) QOL by interfering with daily functioning. Antiemetic guidelines recommend co-administration of a NK1 receptor antagonist (RA)/5-HT3RA/corticosteroid to optimize CINV control in pts at high risk for CINV. NEPA, a fixed combination of the NK1RA netupitant and 5-HT3RA palonosetron (PALO) has shown superior CINV prevention and improvement in QOL over PALO. A single dose of NEPA recently showed non-inferiority to a 3-day aprepitant/granisetron (APR/GRAN) regimen in preventing CINV in the first head-to-head comparison of NK1RA-containing regimens. The impact of CINV on pts’ QOL in this study was explored.
This randomized, double-blind, Phase 3 study in chemotherapy-naïve pts receiving cisplatin-based chemotherapy (CT) assessed the non-inferiority of NEPA versus APR/GRAN for complete response (CR: no emesis/no rescue medication [RM]) rates during the overall (0-120 h) phase post-CT. All pts received dexamethasone on days 1-4. Secondary endpoints included proportion of pts with no emesis, no significant nausea (NSN:
Treatment groups were similar for the 828 pts analyzed: male (71%); mean age 55 years; lung cancer (58%). NIDL rates were higher for NEPA, particularly during the delayed phase; similar results were seen for no emesis, NSN, and no RM.rnTable:
|% Patients||NEPA (N = 412)||APR/GRAN (N = 416)||Risk Difference (95% CI)rn|
|NIDL (overall domain) Acute (0-24h) Delayed (25-120 h)rn||86.2% 76.0%rn||83.2% 70.7%rn||3.3 (-1.6%, 8.1%) 5.8% (-0.1%, 11.8%)rn|
|NIDL (nausea domain) Acute Delayedrn||81.8% 71.1%rn||80.0% 65.1%rn||2.0% (-3.3%, 7.3%) 6.5% (0.2%, 12.8%)*rn|
|NIDL (vomiting domain) Acute Delayedrn||87.9% 81.3%rn||86.8% 77.4%rn||1.4% (-3.1%, 5.9%) 4.5% (-1.0%, 9.9%)rn|
|No Emesis Acute Delayedrn||85.2% 79.4%rn||87.5% 76.2%rn||−2.2% (-6.9%, 2.4%) 3.3% (-2.4%, 8.9%)rn|
|NSN Acute Delayedrn||89.8% 78.2%rn||87.3% 72.8%rn||2.6% (-1.7%, 6.9%) 5.4% (-0.4%, 11.2%)rn|
|No RM Acute Delayedrn||98.8% 97.6%rn||98.3% 94.7%rn||0.5% (-1.2%, 2.1%) 2.9% (0.2%, 5.5%)*rn|
statistically significant difference NEPA: fixed combination netupitant/palonosetron, APR: aprepitant, GRAN: granisetron, NIDL: no impact on daily life, NSN: no significant nausea, RM: rescue medicationrn
In this first study comparing NK1RA regimens, NEPA administered only on day 1 was numerically similar to a 3-day oral APR/GRAN regimen in maintaining functional status in patients receiving highly emetogenic CT.
Clinical trial identification
Legal entity responsible for the study
Helsinn Healthcare, SA
L. Zhang: Consultant for MSD; research funding from MSD and Lilly. S. Lu: Consultant Boehinger and Roche; speaker\'s bureau Lilly; travel expenses from Hutchison and Medipharm Limited. S. Chessari, C. Lanzarotti: Employee: Helsinn Healthcare. K. Jordan: Honorarium/consultant for Helsinn, Tesaro, MDS, and Merck. Travel accommodations from MSD. M. Aapro: Honorarium from Amgen. Consultant for Helsinn, Teva, Hospira, Merck KGaA, Merck, Sandoz, Pierre Fabre, Vifor Pharma, Tesaro. Research funding from Helsinn, Sandoz, Hopsira, Novartis, Pierre Fabre. Expert Testimony for Amgen. All other authors have declared no conflicts of interest.