ent-Reported Outcomes: The impact of nausea and vomiting on patients’ daily lives was assessed in Cycle 1 of both Phase III studies using the Functional Living Index–Emesis (FLIE), a validated nausea- and vomiting-specific patient-reported outcome measure. Minimal or no impact of nausea and vomiting on patients’ daily lives is defined as a FLIE total score >108. In each of the 2 studies, a higher proportion of patients receiving the aprepitant regimen reported minimal or no impact of nausea and vomiting on daily life (Study 1: 74% versus 64%; Study 2: 75% versus 64%).
Multiple-Cycle Extension: In the same 2 clinical studies, patients continued into the Multiple-Cycle extension for up to 5 additional cycles of chemotherapy. The proportion of patients with no emesis and no significant nausea by treatment group at each cycle is depicted in Figure 3. Antiemetic effectiveness for the patients receiving the aprepitant regimen is maintained throughout repeat cycles for those patients continuing in each of the multiple cycles.
Figure 3: Proportion of Patients Receiving Highly Emetogenic Chemotherapy With No Emesis and No Significant Nausea by Treatment Group and Cycle
Moderately Emetogenic Chemotherapy
In a multicenter, randomized, double-blind, parallel-group, clinical study in breast cancer patients, the aprepitant regimen (see table that follows) was compared with a standard of care therapy in patients receiving a moderately emetogenic chemotherapy regimen that included cyclophosphamide 750-1500 mg/m2; or cyclophosphamide 500-1500 mg/m2 and doxorubicin (≤60 mg/m2) or epirubicin (≤100 mg/m2).
In this study, the most common combinations were cyclophosphamide + doxorubicin (60.6%); and cyclophosphamide + epirubicin + fluorouracil (21.6%).
Of the 438 patients who were randomized to receive the aprepitant regimen, 99.5% were women. Of these, approximately 80% were White, 8% Black, 8% Asian, 4% Hispanic, and <1% Other. The aprepitant-treated patients in this clinical study ranged from 25 to 78 years of age, with a mean age of 53 years; 70 patients were 65 years or older, with 12 patients being over 74 years.
Patients (N = 866) were randomized to either the aprepitant regimen (N = 438) or standard therapy (N = 428). The treatment regimens are defined in the table that follows.
Treatment Regimens: Moderately Emetogenic Chemotherapy Trial Treatment Regimen Day 1 Days 2 to 3
1 hour prior to chemotherapy.
30 minutes prior to chemotherapy.
30 to 60 minutes prior to chemotherapy and 8 hours after first ondansetron dose.
Aprepitant Aprepitant 125 mg PO*
Dexamethasone 12 mg PO†
Ondansetron 8 mg PO x 2 doses‡ Aprepitant 80 mg PO Daily
Standard Therapy Dexamethasone 20 mg PO
Ondansetron 8 mg PO x 2 doses Ondansetron 8 mg PO Daily (every 12 hours)
Aprepitant placebo and dexamethasone placebo were used to maintain blinding.
The antiemetic activity of oral aprepitant was eva luated based on the following endpoints:
Primary endpoint:
Complete response (defined as no emetic episodes and no use of rescue therapy) in the overall phase (0 to 120 hours post-chemotherapy)
Other prespecified endpoints:
no emesis (defined as no emetic episodes regardless of use of rescue therapy)
no nausea (maximum VAS <5 mm on a 0 to 100 mm scale)
no significant nausea (maximum VAS <25 mm on a 0 to 100 mm scale)
complete protection (defined as no emetic episodes, no use of rescue ther |
