Comparison of aprepitant combination regimen with 4-day ondansetron + 4-day dexamethasone for prevention of acute and delayed nausea/vomiting after cisplatin chemotherapy

Abstract

8007 Background: Previous studies showed that aprepitant (APR) + ondansetron (OND) + dexamethasone (DEX) provided better control of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in highly emetogenic chemotherapy (HEC) than OND+DEX. However, OND was given only on the day of chemotherapy (Day 1). These studies did not address whether the APR regimen is superior to OND + DEX when both OND and DEX are given on multiple days to control delayed-phase CINV in patients receiving HEC. Methods: This multinational, randomized, double-blind study compared the APR regimen (APR 125 mg + DEX 12 mg + OND 32 mg i.v. on Day 1, APR 80 mg + DEX 8 mg on Days 2–3, DEX 8 mg on Day 4) with the OND regimen (OND 32 mg i.v. + DEX 20 mg on Day 1, OND 8 mg b.i.d. + DEX 8 mg b.i.d. on Days 2–4) in patients receiving their first cycle of cisplatin (≥70 mg/m2). The primary endpoint was complete response (no vomiting & no use of rescue therapy) in the 120-hr period following cisplatin. Multiplicity adjustments were made for the secondary variables complete response in the delayed phase and no vomiting in the delayed and overall phase. Results: Of 489 adults randomized, 484 were included in the modified intention-to-treat efficacy evaluation. Complete response rates were significantly higher for the APR regimen than for the OND regimen for the overall period (0–120 hr), as well as the acute (0–24 hr) and delayed (>24–120 hr) periods (Table). The APR regimen also provided higher rates of no vomiting over 0–120 hr (76.5% vs 62.2%, p ≤0.001), 0–24 hr (88.9% vs 80.5%, p=0.004), and >24–120 hr (79.0% vs 64.3%, p ≤0.001). Conclusions: The APR regimen was superior to the OND regimen as judged by complete response. This study shows that, in the prevention of delayed CINV, the APR regimen is not only superior to 1-day OND + 4-day DEX, as shown in two previous trials, but is also superior to 4-day OND + 4-day DEX. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck Merck Merck