Merck announced today results from a new non-inferiority trial of an antiemetic regimen containing fosaprepitant dimeglumine administered as a single intravenous (IV) 150-mg dose in combination with a 5-HT3 antagonist and dexamethasone compared with a three-day regimen of aprepitant with a 5-HT3 antagonist and dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving a first cycle of cisplatin-based chemotherapy. The regimen containing 150 mg fosaprepitant dimeglumine was not inferior to the regimen with oral aprepitant. Results of the study, known as EASE-017, will be presented on June 8th at the 2010 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, during a discussion on the poster titled "Phase III randomized double-blind study of single-dose fosaprepitant for prevention of cisplatin-induced nausea and vomiting."
"The results of this study demonstrate that an antiemetic-regimen with a single, 150-mg injection of fosaprepitant provides similar protection against CINV as a three-day regimen of oral EMEND® (aprepitant), which has become part of the standard of care for patients receiving highly emetogenic chemotherapy," said Steven Grunberg, M.D., Professor of Medicine and Pharmacology, University of Vermont. "These findings are important because prevention of CINV is a major concern, and this formulation of EMEND could potentially provide dosing flexibility to prevent CINV."
Currently, EMEND is approved as a part of a three-day regimen for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic and highly emetogenic cancer chemotherapy, including high-dose cisplatin.
In the study, 71.9 percent of patients who received an antiemetic regimen that included a single, 150 mg dose of fosaprepitant , ondansetron 32 mg IV, and dexamethasone 12 mg orally on Day 1, and dexamethasone 8 mg orally on Day 2, and dexamethasone 8 mg orally twice daily on Days 3 and 4 achieved a complete response, defined as no vomiting and no use of rescue medication, in the overall phase of chemotherapy (0 to 120 hours post-initiation of cisplatin-based chemotherapy) compared to 72.3 percent of those receiving an antiemetic regimen containing a three-day oral regimen of EMEND (EMEND 125 mg orally, ondansetron 32 mg IV, and dexamethasone 12 mg orally on Day 1, EMEND 80 mg orally once daily on Days 2 and 3, and dexamethasone 8 mg orally once daily on Days 2 through 4; 95 percent confidence interval [CI] for difference between groups = -4.1 to 3.3). In addition, 74.3 percent of patients treated with the regimen containing the single, 150 mg dose of fosaprepitant achieved a complete response in the delayed phase (25 to 120 hours post cisplatin-based chemotherapy), compared to 74.2 percent of patients treated with a regimen containing a three-day regimen of EMEND. (95 percent CI for difference between groups = -3.5 to 3.7).
The overall incidence and types of adverse events were generally consistent between the two treatment groups. The most frequently reported drug-related clinical adverse events in both the group receiving a single, 150 mg dose of fosaprepitant and the group receiving oral EMEND were asthenia (loss of strength), constipation, anorexia, diarrhea and nausea.