Dataset Information

Efficacy of NEPA, a fixed antiemetic combination of netupitant and palonosetron, vs a 3-day aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting (CINV) in Chinese patients receiving highly emetogenic chemotherapy (HEC) in a randomized Phase 3 study.

ABSTRACT: NEPA is the only fixed combination antiemetic, comprised of an NK₁ RA (netupitant) and a 5-HT₃ RA (palonosetron). In the first head-to-head trial to compare NK₁ RA-containing regimens, a single oral dose of NEPA was non-inferior to a 3-day aprepitant/granisetron (APR/GRAN) regimen for the primary endpoint of overall (0-120 hours) complete response (no emesis/no rescue). This pre-specified analysis evaluates the efficacy of NEPA versus APR/GRAN in the subset of Chinese patients in the study. In addition, efficacy in patients at greatest emetic risk receiving high-dose cisplatin (≥70 mg/m² ) was explored. Chemotherapy-naïve patients with solid tumors in this randomized, double-blind study received either a single dose of NEPA prior to cisplatin-based chemotherapy or a 3-day regimen of APR/GRAN, both with dexamethasone on Days 1-4. Efficacy was evaluated through complete response, no emesis, and no significant nausea rates during the acute (0-24 hours), delayed (25-120 hours) and overall phases as well as individual days post-chemotherapy, as the daily course of CINV protection is often unstudied. The Chinese subset included 667 patients; of these, 363 (54%) received high-dose cisplatin. Baseline characteristics were comparable. While response rates were similar for NEPA and APR/GRAN during the acute, delayed and overall phases, significantly fewer NEPA patients experienced breakthrough CINV on individual Days 3-5 in both the Chinese patients and also in those receiving high-dose cisplatin. As a fixed oral NK₁ RA/5HT₃ RA combination given once/cycle, NEPA is a convenient highly effective prophylactic antiemetic that may offer better protection from CINV than a 3-day APR/GRAN regimen on Days 3-5 following highly emetogenic chemotherapy.

SUBMITTER: Chang J

PROVIDER: S-EPMC7367622 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Efficacy of NEPA, a fixed antiemetic combination of netupitant and palonosetron, vs a 3-day aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting (CINV) in Chinese patients receiving highly emetogenic chemotherapy (HEC) in a randomized Phase 3 study.

Chang Jianhua J Chen Gongyan G Wang Dong D Wang Guihua G Lu Shun S Feng Jifeng J Li Wei W Li Ping P Lanzarotti Corinna C Chessari Salvatore S Zhang Li L

Cancer medicine 20200530 14

NEPA is the only fixed combination antiemetic, comprised of an NK1 RA (netupitant) and a 5-HT3 RA (palonosetron). In the first head-to-head trial to compare NK1 RA-containing regimens, a single oral dose of NEPA was non-inferior to a 3-day aprepitant/granisetron (APR/GRAN) regimen for the primary endpoint of overall (0-120 hours) complete response (no emesis/no rescue). This pre-specified analysis evaluates the efficacy of NEPA versus APR/GRAN in the subset of Ch ...[more]

PMID: 32472742

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Project description:BackgroundCo-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.Patients and methodsThis 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).ResultsTreatment 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.ConclusionsIn 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.

Project description:BackgroundNeurokinin (NK) 1 receptor antagonists (RAs), administered in combination with a 5-hydroxytryptamine-3 (5-HT3 ) RA and dexamethasone (DEX), have demonstrated clear improvements in chemotherapy-induced nausea and vomiting (CINV) prevention over a 5-HT3 RA plus DEX. However, studies comparing the NK1 RAs in the class are lacking. A fixed combination of a highly selective NK1 RA, netupitant, and the 5-HT3 RA, palonosetron (NEPA), simultaneously targets two critical antiemetic pathways, thereby offering a simple convenient antiemetic with long-lasting protection from CINV. This study is the first head-to-head NK1 RA comparative study in patients receiving anthracycline cyclophosphamide (AC) and non-AC moderately emetogenic chemotherapy (MEC).Materials and methodsThis was a pragmatic, multicenter, randomized, single-cycle, open-label, prospective study designed to demonstrate noninferiority of single-dose NEPA to a 3-day aprepitant regimen in preventing CINV in chemotherapy-naive patients receiving AC/non-AC MEC in a real-life setting. The primary efficacy endpoint was complete response (no emesis/no rescue) during the overall (0-120 hour) phase. Noninferiority was achieved if the lower limit of the 95% confidence interval (CI) of the difference between NEPA and the aprepitant group was greater than the noninferiority margin set at -10%.ResultsNoninferiority of NEPA versus aprepitant was demonstrated (risk difference 9.2%; 95% CI, -2.3% to 20.7%); the overall complete response rate was numerically higher for NEPA (64.9%) than aprepitant (54.1%). Secondary endpoints also revealed numerically higher rates for NEPA than aprepitant.ConclusionThis pragmatic study in patients with cancer receiving AC and non-AC MEC revealed that a single dose of oral NEPA plus DEX was at least as effective as a 3-day aprepitant regimen, with indication of a potential efficacy benefit for NEPA.Implications for practiceIn the absence of comparative neurokinin 1 (NK1 ) receptor antagonist (RA) studies, guideline committees and clinicians consider NK1 RA agents to be interchangeable and equivalent. This is the first head-to-head study comparing one NK1 RA (oral netupitant/palonosetron [NEPA]) versus another (aprepitant) in patients receiving anthracycline cyclophosphamide (AC) and non-AC moderately emetogenic chemotherapy. Noninferiority of NEPA versus the aprepitant regimen was demonstrated; the overall complete response (no emesis and no rescue use) rate was numerically higher for NEPA (65%) than aprepitant (54%). As a single-dose combination antiemetic, NEPA not only simplifies dosing but may offer a potential efficacy benefit over the current standard-of-care.

Project description:BackgroundDespite significant progress in the prevention of chemotherapy-induced nausea and vomiting (CINV) by using dexamethasone combined with palonosetron for patients who received moderate-emetogenic chemotherapy (MEC), some of these patients still suffer from CINV. We evaluated whether aprepitant combined with palonosetron can improve the efficacy in the prevention of CINV in patients receiving MEC.MethodsThis was a single-centre, open-label, phase III, randomized controlled trial, which was done at the Sixth Affiliated Hospital of Sun Yat-sen University of China. The registered patients planned to receive mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil) but had not received any chemotherapy previously. The patients were randomized in a 1:1 ratio to the aprepitant group (aprepitant 125 mg orally on day 1, 80 mg on day 2-3) and the dexamethasone group (dexamethasone 10 mg intravenously on day 1, 5 mg on days 2 and 3), both groups with palonosetron 0.25 mg intravenously on day 1. The primary endpoint was the proportion of patients who achieved a complete response (CR), defined as the absence of vomiting and no use of rescue medications in the overall phase (0-120 h). The primary outcome and safety were assessed in the modified intention-to-treat population, which excluded all patients who used estazolam within 24 h before registration and those who refused to keep a diary documenting the severity of nausea, frequency of vomiting, and the use of rescue therapy. This trial is registered with ClinicalTrials.gov, NCT02909478.FindingsBetween Sep 1, 2017, and Oct 23, 2019, 320 patients were enrolled, and 315 patients were evaluated. The proportion of patients who achieved CR was significantly higher with aprepitant than that noted with dexamethasone in the overall phase (88.8% vs. 74.2%; P = 0.0010; rate difference, RD 15%, 95% CI, 6% to 23%) and in the delayed phase (25-120 h), 90.6% vs. 75.5%, (P < 0.0001; RD 15%, 95%CI, 7% to 23%). No significant difference of CR rate was observed in the acute phase (0-24 h), 93.8% vs. 93.5%, (P = 0.94; RD 0%, 95% CI, -5% to 6%)). In the overall phase, the incidence of insomnia (P < 0.0010), dyspepsia (P = 0.038), and flushing (P = 0.0010) reported by the patients was significantly higher in the dexamethasone group than that in the aprepitant group.InterpretationAprepitant combined with palonosetron is superior to dexamethasone combined with palonosetron in patients who received the MEC regimen mFOLFOX6 in terms of preventing CINV.FundingThe National Key R&D Program of China (2019YFC1316000) and the National Natural Science Foundation of China (81974369).

Dataset Information

Efficacy of NEPA, a fixed antiemetic combination of netupitant and palonosetron, vs a 3-day aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting (CINV) in Chinese patients receiving highly emetogenic chemotherapy (HEC) in a randomized Phase 3 study.

Publications

Efficacy of NEPA, a fixed antiemetic combination of netupitant and palonosetron, vs a 3-day aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting (CINV) in Chinese patients receiving highly emetogenic chemotherapy (HEC) in a randomized Phase 3 study.

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