Efficacy and safety of rolapitant, a novel NK-1 receptor antagonist, for the prevention of chemotherapy-induced nausea and vomiting in subjects receiving highly emetogenic chemotherapy.

Abstract

9077 Background: Management of chemotherapy-induced nausea and vomiting (CINV) improves quality of life and increases the likelihood that patients will continue to receive appropriate treatment. The objective of this dose finding study was to evaluate rolapitant for the prevention of CINV in subjects receiving highly emetogenic chemotherapy (HEC). Methods: A phase II, double blind study in which 454 subjects receiving HEC (≥70mg/m2 cisplatin-based chemotherapy) were randomized in equal fashion prior to chemotherapy to receive ondansetron + dexamethasone + either placebo or 10, 25, 100 or 200mg of rolapitant. Subjects recorded episodes of emesis, severity of nausea, and use of rescue medication(s) daily within a subject diary from Days 1 through 6 of Cycle 1. Results: The rolapitant 200mg group had significantly greater complete response rates (no emesis and no use of rescue medication) in the overall (0 to 120 hours), acute (0 to ≤24 hours) and delayed (>24 to 120 hours) phases compared to the placebo group (62.5% vs. 46.7%, p=0.032; 87.6% vs. 66.7%, p=0.001 and 63.6% vs. 48.9%, p=0.045, respectively). Moreover, the 200mg group had significantly greater rates of no emesis and no significant nausea in the overall, acute, and delayed phases and achieved statistically significant better QoL scores (FLIE questionnaire) compared to the placebo group. Rates for no emesis and no significant nausea for the 200mg dose group in Cycles 2 to 6 continued to demonstrate superior treatment effect vs. placebo. Treatment-related adverse events were mild and included constipation, headache, fatigue and dizziness. Overall, serious adverse events (SAEs) occurred with similar incidences across all treatment groups (9% - 14%). Most common SAEs were febrile neutropenia, neutropenia, vomiting, dehydration, nausea and pneumonia and were considered related to chemotherapy or underlying cancer and not to rolapitant. Conclusions: Administration of rolapitant 200mg with ondansetron and dexamethasone is safe and effective at preventing CINV in subjects receiving HEC.