1337PD - Effects of patient characteristics on the efficacy and safety of aprepitant in a pediatric population

Date 29 September 2014
Event ESMO 2014
Session Supportive and palliative care
Topics Anti-Cancer Agents & Biologic Therapy
Supportive Care
Cancer in Special Situations
Presenter Christian Zwaan
Citation Annals of Oncology (2014) 25 (suppl_4): iv471-iv477. 10.1093/annonc/mdu350
Authors C. Zwaan1, S. Loftus2, A. Taylor3, C. Dicristina4, S. Green5, H.J. Kang6
  • 1Pediatric Oncology, Erasmus MC, 3015GJ - Rotterdam/NL
  • 2Respiratory And Immunology, Merck & Co., Inc., North Wales/US
  • 3Biostatistics And Research Decision Sciences, Merck & Co., Inc., Upper Gwynedd/US
  • 4Clinical Development Execution Organization, Merck & Co., Inc., North Wales/US
  • 5Clinical Research, Merck Research Laboratories, Kenilworth/US
  • 6Pediatrics, Seoul National University College of Medicine, Seoul National University Hospital, Seoul/KR

Abstract

Aim

This phase III, randomized, double-blind, active-comparator trial (NCT01362530) evaluated the safety and efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) in children.

Methods

Patients 12-17 years (y) old undergoing highly/moderately emetogenic (guideline based) chemotherapy (chemo) received aprepitant capsule 125 mg + ondansetron before chemo (Day 1) + aprepitant capsule 80 mg (Days 2-3), OR placebo (Days 1-3) + ondansetron (Day 1). Patients <12 y old received aprepitant powder-for-suspension (PFS) 3 mg/kg (up to 125 mg) + ondansetron (Day 1) + aprepitant PFS 2 mg/kg (up to 80 mg) (Days 2-3), OR placebo (Days 1-3) + ondansetron (Day 1). Dexamethasone was added at the investigator's discretion. Aprepitant and control regimens were compared for complete response (CR: no vomiting/retching/rescue medication) 25-120 hours (h) after chemo initiation (delayed phase; primary objective). The current analysis examined the CR in each phase (acute [0-24 h], delayed, overall [0-120 h]) across various subgroups including age, dexamethasone use, and use of very highly emetogenic chemo (VHEC).

Results

A total of 302 patients participated (ages 6 months to <2 y, n = 35; 2 to <6 y, n = 88; 6 to <12 y, n = 84; and 12 to 17 y, n = 95); 152 received the aprepitant regimen and 150 received control. During the delayed phase, the proportion of patients achieving CR varied across age groups within each regimen but was higher for aprepitant (range, 46.3%-55.6%) vs control (range, 10.4%-37.2%). A greater proportion of patients achieved CR with aprepitant vs control regardless of dexamethasone use (yes, 36.4% vs 21.4%; no, 56.5% vs 27.8%). In addition, CR rate was higher for aprepitant vs control in those receiving VHEC (42.4% vs 19.8%). Similar patterns were observed during the acute and overall phases. The aprepitant regimen was well tolerated; adverse events were similar between regimens and consistent with those in patients undergoing chemo.

Conclusions

The addition of aprepitant to a 5HT3-antagonist (± dexamethasone) as part of a 3-day regimen was well tolerated and effective for reducing CINV in pediatric patients with cancer, regardless of age, dexamethasone use, and use of VHEC.

Disclosure

S. Loftus: Full-time employee of Merck & Co., Inc., with stock ownership; A. Taylor: Full-time employee of Merck & Co., Inc.; C. Dicristina: Full-time employee of Merck & Co., Inc.; S. Green: Full-time employee of Merck & Co., Inc., with stock ownership; H.J. Kang: Have received research funding from Merck & Co., Inc. (MK869 PN208 Study involvement). All other authors have declared no conflicts of interest.