MASCC/ISOO 2015: Phase III Study of Single-Dose Fosaprepitant Dimeglumine in Prevention of Chemotherapy-Induced Nausea and Vomiting
Researchers from Merck presented results from a phase III study investigating the safety and efficacy of single-dose fosaprepitant dimeglumine (Emend) for injection, a neurokinin-1 receptor antagonist, in combination with other antivomiting medicines, for the prevention of chemotherapy-induced nausea and vomiting in adult cancer patients receiving moderately emetogenic chemotherapy. In the study, the single-dose fosaprepitant dimeglumine regimen provided greater protection from nausea and vomiting following administration of chemotherapy vs an active control of placebo with other antivomiting medicines. These data were presented at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) Annual Meeting (Abstract #27-02-O) in Copenhagen, Denmark.
“The results from this important phase III trial are very encouraging as they … show the potential to use a single-day antiemetic regimen,” said Bernardo L. Rapoport, MD, Chief Medical Oncologist, Medical Oncology Centre of Rosebank, in Johannesburg, South Africa.
“Nausea and vomiting remain a significant burden for patients receiving chemotherapy, and we look forward to submitting these data for [fosaprepitant dimeglumine] to the U.S. Food and Drug Administration,” said Stuart Green, Vice President, Clinical Research, Merck Research Laboratories.
In the United States, the single-dose regimen of fosaprepitant dimeglumine is approved for use associated with highly emetogenic chemotherapy, including high-dose cisplatin, in combination with other antiemetic agents.
Study Background
In this global randomized, phase III, double-blind study, more than 1,000 patients receiving moderately emetogenic chemotherapy were randomly assigned to receive either single-dose fosaprepitant dimeglumine for injection (150 mg) in combination with ondansetron capsules (16 mg) and dexamethasone capsules (12 mg) (n = 504) on day 1 (followed by oral placebo for ondansetron on days 2 and 3), or an active control regimen consisting of placebo (intravenous saline) in combination with ondansetron (16 mg) and dexamethasone (20 mg) (n = 497) on day 1 (followed by 8 mg of ondansetron on days 2 and 3).
The primary endpoint of the study was complete response (as measured by no vomiting and no use of rescue medication for nausea or vomiting) in the delayed phase (25 to 120 hours following initiation of chemotherapy). The secondary endpoints were complete response after the first dose of chemotherapy in the acute phase (0 to 24 hours) and in the overall phase (0 to 120 hours), as well as no vomiting in the overall phase.
Efficacy Findings
For the primary study endpoint, the fosaprepitant dimeglumine regimen provided a higher incidence of complete response on days 2 through 5, with a complete response observed in 78.9% of patients receiving the fosaprepitant dimeglumine regimen vs 68.5% in the active control group (P < .001). For the secondary endpoints, in the acute phase, complete response was observed in 93.2% of patients receiving the fosaprepitant dimeglumine regimen vs 91% in the active control group (P = .184).
Overall, complete response was observed in 77.1% of patients receiving the fosaprepitant dimeglumine regimen vs 66.9% in the active control group (P < .001). Additionally, a significantly greater proportion of patients receiving the fosaprepitant dimeglumine experienced no vomiting overall (82.7% with fosaprepitant dimeglumine vs 72.9% in the active control group, P < .001) and in the delayed phase (83.9% with fosaprepitant dimeglumine vs 75.1% in the active control group, P < .001), with a favorable trend in the acute phase (94.8% with fosaprepitant dimeglumine vs 92% in the active control group).
The most common adverse events in patients receiving the fosaprepitant dimeglumine regimen and active control group included fatigue (15.1% and 12.9%), diarrhea (12.7% and 11.3%), and constipation (9.3% and 10.5%). Treatment-related adverse events were observed in 8.5% of patients receiving fosaprepitant dimeglumine and in 9.1% of patients in the active control group. Serious treatment-related adverse events were observed in 0.2% of patients receiving fosaprepitant dimeglumine and in 0.4% of patients in the active control group.
MASCC/ISOO abstracts are available here.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
