A single intravenous dose of fosaprepitant dimeglumine was shown to be superior to placebo when either were combined with other anti-vomiting agents for protection against chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy.
A single intravenous dose of the antiemetogenic agent fosaprepitant dimeglumine (EMEND for Injection) was shown to be superior to placebo when either were combined with other anti-vomiting agents for protection against chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC), according to findings from a phase III trial.
The data were presented during an oral session at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) 2015 Annual Meeting held June 25-27 in Copenhagen, Denmark.
Bernardo L. Rapoport, MD, chief medical oncologist at the Medical Oncology Centre of Rosebank, Johannesburg, South Africa and the study’s principal investigator, said in a statement that the results of this trial are especially encouraging because, “they are the first study to evaluate EMEND for Injection in a combination regimen for the prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy and show the potential to use a single-day antiemetic regimen.”
Fosaprepitant is a water-soluble P/neurokinin (NK-1) receptor antagonist approved in several other countries for administration as a single IV dose to prevent nausea and vomiting associated with both highly emetogenic chemotherapy (HEC) and MEC. In the United States, however, the single-dose, 150-mg IV administration is currently approved only to prevent acute and delayed nausea and vomiting associated with HEC, whereas the 3-day dosing regimen is approved in both the HEC and MEC settings. The 3-day dosing regimen is comprised of 115 mg EMEND for Injection on day 1, followed by an 80-mg oral EMEND capsule on days 2 and 3.
The multinational, randomized, double-blind, parallel-group trial reported at the MASCC/ISOO meeting involved 1011 HEC- and MEC-naïve adult patients who were scheduled to receive one or more MEC agents. Patients in the fosaprepitant cohort (n = 497) were assigned to receive a single dose of 150 mg IV fosaprepitant plus 16 mg of ondansetron (two 8-mg capsules, one administered 30 minutes prior to, and the other 8 hours after, the first dose of MEC) and three, 4-mg dexamethasone capsules on the first day of their MEC treatment.
Patients in the active control group (n = 504) were given a saline IV placebo in place of the fosaprepitant, an ondansetron regimen equivalent to the experimental arm, and 20 mg of dexamethasone on day 1. Patients in the fosaprepitant arm received placebo capsules in place of the 8-mg daily dose of oral ondansetron patients in the control group received on days 2 and 3.
Complete response (CR), defined as no vomiting or use of rescue medication 25 to 120 hours after MEC (the delayed phase) was the study’s primary endpoint. Secondary outcomes were CR 0-24 hours post-MEC (the acute phase) and overall (0-120 hours after MEC).
During the delayed phase of treatment, a CR was seen in 78.9% of patients in the fosaprepitant arm, compared with 68.5% in the control group (P <.001). During the acute phase, 93.2% of patients receiving fosaprepitant experienced a CR, versus 91% among active controls (P = .184). Overall, 0-120 hours after MEC, CR was achieved in 77.1% of patients in the experimental arm, compared with 66.9% in the active control group (P <.001), and a significantly greater proportion of patients receiving fosaprepitant experienced no vomiting (82.7%) versus controls (72.9%), according to results released by Merck, the drug’s manufacturer. The no vomiting benefit was also observed during the delayed (83.9% with fosaprepitant vs 75.1% with controls) and acute (94.8% vs 92%) phases.
The most common all-grade adverse events (AEs) among patients receiving the fosaprepitant regimen versus active controls included fatigue (15.1% and 12.9%), diarrhea (12.7% and 11.3%), and constipation (9.3% and 10.5%). Treatment-related AEs were observed in 8.5% of patients receiving the forsaprepitant regimen and in 9.1% of controls. Serious treatment-related AEs were seen in 0.2% of patients receiving the fosaprepitant regimen and in 0.4% of patients in the active control group.
Merck also announced that it plans to submit these data to the FDA in the second half of this year to obtain approval of the single-dose EMEND for Injection regimen to prevent CINV in the MEC setting.
Rapoport B, Weinstein C, Camacho ES, et al. A randomized, phase III, double-blind study of intravenous fosaprepitant as a single dose for preventing chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy. Presented at: MASCC/ISOO Annual Meeting on Supportive Care in Cancer June 25-27, 2015; Copenhagen, Denmark. Abstract 27-02-O.