Assessing duration of breakthrough chemotherapy-induced nausea and vomiting (CINV): A pooled study analysis of NEPA versus aprepitant.

Abstract

12091 Background: The historical standard clinical trial endpoint for preventing chemotherapy-induced nausea and vomiting (CINV) has been assessment of complete response (CR: no emesis and no rescue medication use) over five days. Recent evaluations focused on the duration of breakthrough CINV suggest that long duration of CINV results in more lost work time and impaired activity and is also a strong predictor for CINV in subsequent cycles. A recent pooled analysis of three similarly designed registration trials of NEPA, a fixed oral combination NK1 receptor antagonist (RA) (netupitant)/5-HT3RA (palonosetron), showed significantly higher CR rates during the delayed phase (≥24-120h) for NEPA compared to an aprepitant (APR) regimen. In this post-hoc analysis, we evaluated the extent and duration of breakthrough CINV in these pooled studies. Methods: Chemotherapy-naïve patients who received cisplatin-based chemotherapy and antiemetic prophylaxis of either a single dose of NEPA plus dexamethasone (DEX) or a 3-day APR/5-HT3 RA/DEX regimen from three randomized, double-blind pivotal trials were included. Patients without a CR were defined as treatment failures. Extent of CINV was evaluated using proportions of patients with treatment failure, emesis, and significant nausea (defined as >25 mm on a 100 mm visual analog scale). Over the 5-day overall phase, duration was categorized as 1-2, and ≥3 days. Pearson’s chi-square test was employed to compare risks between treatments for each duration category in each of the previously mentioned endpoints. Results: Among all 621 NEPA and 576 APR patients, a significantly greater proportion of APR patients experienced treatment failure, emesis, and significant nausea for ≥3 days. Specifically, among patients with treatment failure, 31% (41/134) who received NEPA and 43% (61/143) who received APR experienced breakthrough CINV for ≥3 days. Conclusions: Expanding on data suggesting single-day NEPA is more effective than 3-day APR in preventing delayed CINV, NEPA is also more effective in minimizing the extent and duration of CINV in patients with breakthrough emesis and nausea.[Table: see text]