Addition of Aprepitant to Ondansetron Effective in Preventing Chemotherapy-Induced Nausea and Vomiting in Pediatric Patients
In a phase III trial reported in The Lancet Oncology, Kang et al found that adding aprepitant to ondansetron with or without dexamethasone was effective in preventing chemotherapy-induced nausea and vomiting in pediatric patients receiving moderately or highly emetogenic chemotherapy.
Study Details
In this double-blind trial, 302 patients with documented malignancy aged 6 months to 17 years from 49 sites in 24 countries scheduled to receive either moderately or highly emetogenic chemotherapy were randomly assigned between September 2011 and August 2013 to receive aprepitant plus ondansetron (n = 152) or ondansetron plus placebo (n = 150) with or without dexamethasone. Regimens consisted of aprepitant (125 mg for ages 12 to 17 years or 3.0 mg/kg up to 125 mg for ages 6 months to < 12 years) plus ondansetron on day 1, followed by aprepitant (80 mg for ages 12 to 17 years or 2.0 mg/kg up to 80 mg for ages 6 months to < 12 years) on days 2 and 3 or placebo plus ondansetron on day 1 followed by placebo on days 2 and 3.
The primary endpoint was complete response, defined as no vomiting, no retching, and no use of rescue medication during hours 25 to 120 (delayed phase) after initiation of emetogenic chemotherapy. Analyses were performed in patients who received at least one dose of study treatment.
The aprepitant and control groups were generally balanced for age distribution, sex (53% male in both), ethnicity (78% and 73% white, 7% and 11% Asian), receipt of very highly emetogenic chemotherapy (65% and 67%), use of dexamethasone (28% and 29%), and other baseline characteristics.
Complete Response Rates
Complete response in the delayed phase was observed in 51% of the aprepitant group vs 26% of patients in the control group (P < .0001). Complete response was also more common in the aprepitant group during the acute phase (66% vs 52%, P = .0135) and overall (40% vs 20%, P = .0002).
Absence of vomiting was more common in the aprepitant group during the delayed phase (55% vs 28%, P < .0001), acute phase (71% vs 53%, P = .0023), and overall (47% vs 21%, P < .0001). Time to rescue medication was significantly prolonged in the aprepitant group (P = .0024), with 68% vs 52% being free of rescue medication use at 98 hours.
Adverse Events
The most common grade 3 or 4 adverse events were febrile neutropenia (15% in the aprepitant group vs 14% in the control group), anemia (9% vs 17%), and neutropenia (7% vs 11%). Drug-related adverse events were reported in 3% of the aprepitant group and 2% of the control group, with serious drug-related events in 1% vs 0%.
The investigators concluded: “Addition of aprepitant to ondansetron with or without dexamethasone is effective for the prevention of chemotherapy-induced nausea and vomiting in paediatric patients being treated with moderately or highly emetogenic chemotherapy.”
Stuart Green, MD, of Merck & Co, Inc, is the corresponding author for the Lancet Oncology article.
The study was funded by Merck & Co, Inc. For full disclosures of the study authors, visit www.thelancet.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
