A Pragmatic Study Evaluating NEPA Versus Aprepitant for Prevention of Chemotherapy‐Induced Nausea and Vomiting in Patients Receiving Moderately Emetogenic Chemotherapy

Zelek, Laurent; Debourdeau, Philippe; Bourgeois, Hugues; Wagner, Jean Philippe; Brocard, Fabien; Lefeuvre‐Plesse, Claudia; Chauffert, Bruno; Leheurteur, Marianne; Bachet, Jean‐Baptiste; Simon, Hélène; Mayeur, Didier; Scotté, Florian

BACKGROUND: Neurokinin (NK) 1 receptor antagonists (RAs), administered in combination with a 5‐hydroxytryptamine‐3 (5‐HT(3)) RA and dexamethasone (DEX), have demonstrated clear improvements in chemotherapy‐induced nausea and vomiting (CINV) prevention over a 5‐HT(3)RA plus DEX. However, studies comparing the NK(1)RAs in the class are lacking. A fixed combination of a highly selective NK(1)RA, netupitant, and the 5‐HT(3)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 NK(1)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 (NK(1)) receptor antagonist (RA) studies, guideline committees and clinicians consider NK(1)RA agents to be interchangeable and equivalent. This is the first head‐to‐head study comparing one NK(1)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.