CHICAGO—Findings of a new study suggest that an antiemetic regimen containing a single intravenous (IV) 150- mg dose of fosaprepitant dimeglumine in combination with a 5-hydroxytryptamine type 3 (5-HT3) antagonist and dexamethasone appears to be comparable with a 3-day regimen of aprepitant with a 5-HT3 antagonist and dexa methasone for the prevention of chemo - therapy-induced nausea and vomiting (CINV).
The findings from the Evaluation of Fosaprepitant in Single-dose Schedule (EASE)-017 study, which were presented at the 46th annual meeting of the American Society of Clinical Oncology, showed that the regimen containing 150-mg fosaprepitant dimeglumine was not inferior to the regimen with oral aprepitant.
“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 3-day regimen of oral aprepitant, which has become part of the standard of care for patients receiving highly emetogenic chemo - therapy,” said lead study investigator Steven Grunberg, MD, a professor of medicine and pharmacology at the University of Vermont, Burlington. “These findings are important because prevention of CINV is a major concern, and this formulation of aprepitant could potentially provide dosing flexibility to prevent CINV.”
Currently, aprepitant is approved as a part of a 3-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 this phase 3, randomized, double- blind, parallel-group, noninferiority study, researchers studied 2322 patients, all of whom were naïve to cisplatin therapy and were scheduled to receive cisplatin-based chemotherapy at a dose of 70 mg/m2 or higher. Of the patients randomized, 2247 patients were included in the analysis. The study’s primary end point was the proportion of patients who reported no vomiting and no use of rescue therapy (complete response) in the overall phase (0-120 hours after initiation of cisplatin-based chemotherapy). The secondary end point was the proportion of patients who reported a complete response (no vomiting and no use of rescue therapy) in the delayed phase (25-120 hours after initiation of cisplatin-based chemotherapy).
The investigators found that 71.9% of patients who received an antiemetic regimen that included a single, 150-mg dose of fosaprepitant plus 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 in the overall phase of chemotherapy (0- 120 hours after initiation of cisplatin chemotherapy). That was comparable with the 72.3% of those receiving an antiemetic regimen containing a 3-day oral regimen of fosaprepitant (fosaprepitant 125 mg orally, ondansetron 32 mg IV, and dexamethasone 12 mg orally on day 1, fosaprepitant 80 mg orally once daily on days 2 and 3, and dexamethasone 8 mg orally once daily on days 2 through 4).
In addition, 74.3% of patients treated with the regimen containing the single, 150-mg dose of fosaprepitant achieved a complete response in the delayed phase (25-120 hours after cisplatin- based chemotherapy), compared with 74.2% of patients treated with a regimen containing a 3-day dose of fosaprepitant.
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 aprepitant were asthenia, constipation, anorexia, diarrhea, and nausea.
“With the intravenous treatment, there was some venous irritation, but the numbers were very small,” said Grunberg in an interview with The Oncology Pharmacist. “In terms of efficacy, there is equivalence. With the single dose, it is going to add convenience because the patients won’t have to take the pills at home. A lot of policies require preauthorization and, if there is just one single IV, there are no pills going home so there is no authorization and so it is a benefit to the patient. There is also benefit for the office because they are sure the patient is compliant and they don’t have to deal with getting preauthorization for getting a tripack. So, there are economic, social, and medical advantages with this single dose.”