Laurent Zelek1, Philippe Debourdeau2, Hugues Bourgeois3, Jean Philippe Wagner4, Fabien Brocard5, Claudia Lefeuvre-Plesse6, Bruno Chauffert7, Marianne Leheurteur8, Jean-Baptiste Bachet9, Hélène Simon10, Didier Mayeur11, Florian Scotté12. 1. Hôpital Avicenne, Bobigny, France. 2. Institut Sainte-Catherine, Avignon, France. 3. Clinique Victor Hugo, Le Mans, France. 4. Institut Andrée Dutreix and Clinique de Flandre, Dunkerque, France. 5. Polyclinique De Gentilly, Nancy, France. 6. Centre Eugène Marquis, Rennes Cedex, France. 7. Centre Hospitalier Universitaire Amiens, Amiens, France. 8. Centre Henri Becquerel, Rouen, France. 9. Hôpital La Pitié Salpêtrière, Paris, France. 10. Centre Hospitalier Universitaire Morvan, Brest, France. 11. Centre George Francois Leclerc, Dijon, France. 12. Interdisciplinary Cancer Course Department, Gustave Roussy Cancer Center, Villejuif, France.
Abstract
BACKGROUND:Neurokinin (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 METHODS: This 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%. RESULTS: Noninferiority 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. CONCLUSION: This 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 PRACTICE: In 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.
RCT Entities:
BACKGROUND: Neurokinin (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 METHODS: This 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-ACMEC 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%. RESULTS: Noninferiority 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. CONCLUSION: This pragmatic study in patients with cancer receiving AC and non-ACMEC 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 PRACTICE: In 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.
Authors: Alessandro Parisi; Riccardo Giampieri; Alex Mammarella; Cristiano Felicetti; Lisa Salvatore; Maria Bensi; Maria Grazia Maratta; Antonia Strippoli; Roberto Filippi; Maria Antonietta Satolli; Angelica Petrillo; Bruno Daniele; Michele De Tursi; Pietro Di Marino; Guido Giordano; Matteo Landriscina; Pasquale Vitale; Ina Valeria Zurlo; Emanuela Dell'Aquila; Silverio Tomao; Ilaria Depetris; Francesca Romana Di Pietro; Federica Zoratto; Davide Ciardiello; Maria Vittoria Pensieri; Ornella Garrone; Barbara Galassi; Claudio Ferri; Rossana Berardi; Michele Ghidini Journal: Front Oncol Date: 2022-08-12 Impact factor: 5.738