Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: results of a randomized, double-blind phase III trial
Cet essai international de phase III analyse l'efficacité du fosaprépitant en dose unique administrée par voie veineuse pour prévenir les nausées et vomissements induits par une chimiothérapie modérément émétisante
Background : To establish the role of antiemetic therapy with neurokinin-1 (NK1) receptor antagonists (RA) in non–anthracycline and cyclophosphamide (AC)-based moderately emetogenic chemotherapy (MEC) regimens, this study evaluated single-dose intravenous (IV) fosaprepitant for prevention of chemotherapy-induced nausea and vomiting (CINV) associated with non-AC MEC. Patients and methods : In this international, phase III, double-blind trial, adult cancer subjects scheduled to receive ≥1 non-AC MEC on day 1 were randomized to a regimen comprising single-dose IV fosaprepitant 150 mg or placebo along with ondansetron and dexamethasone on day 1; control regimen recipients received ondansetron on days 2 and 3. Primary endpoints were the proportion of subjects achieving a complete response (CR; no vomiting and no use of rescue medication) in the delayed phase (25–120 hours after MEC initiation) and safety. Secondary endpoints included CR in the overall and acute phases (0–120 and 0–24 hours after MEC initiation, respectively) and no vomiting in the overall phase. Nausea and the Functional Living Index-Emesis [FLIE] were assessed as exploratory endpoints. Results : The fosaprepitant regimen improved CR significantly in the delayed (78.9% versus 68.5%; P<0.001) and overall (77.1% versus 66.9%; P<0.001) phases, but not in the acute phase (93.2% versus 91.0%; P=0.184), versus control. In the overall phase, the proportion of subjects with no vomiting (82.7% versus 72.9%; P<0.001) and no significant nausea (83.2% versus 77.9%; P=0.030) were also significantly improved with the fosaprepitant regimen. The fosaprepitant regimen was generally well tolerated. Conclusion : Single-dose fosaprepitant added to a 5-HT3 RA and dexamethasone was well tolerated and demonstrated superior control of CINV (primary endpoint achieved) associated with non-AC MEC. This is the first study to evaluate NK1 RA therapy as an IV formulation in a well-defined non-AC MEC population.