Exploration of the heterogeneity of moderately emetogenic chemotherapy on response to fosaprepitant in a randomized phase 3 trial

Background

A single-day triple-antiemetic fosaprepitant (FA) regimen demonstrated superiority to a standard 3-day regimen for preventing chemotherapy induced nausea and vomiting (CINV) in subjects receiving nonanthracycline and cyclophosphamide (AC)-based moderately emetogenic chemotherapy (MEC). However, the impact of MEC emetogenicity and duration of chemotherapy warrants exploration.

Methods

This was a phase 3, global, randomized, double-blind, parallel-group study in adults scheduled to receive an IV dose of ≥1 MEC agents on treatment day 1. Subjects were randomly assigned 1:1 to a control or FA regimen. The control regimen consisted of 8 mg oral ondansetron, 20 mg dexamethasone, and IV saline as placebo before the first dose of MEC on day 1, and 8 mg oral ondansetron 8 hours after the first dose, and every 12 hours on days 2 and 3. The FA regimen consisted of the same dose of oral ondansetron on day 1, along with 12 mg dexamethasone and a single dose of 150 mg IV FA before the first dose of MEC on day 1, with no additional prophylactic antiemetic beyond day 1. Primary endpoint was complete response (CR; no vomiting or rescue medication) in the delayed phase (0 to 120 hours following MEC).

Results

Overall, 1000 subjects were included in the intent-to-treat treat population (FA: n = 502; Control: n = 498). The primary endpoint was met (P 

Conclusions

A single-day FA regimen is effective for preventing CINV in subjects receiving non-AC MEC with/without carboplatin and in both single- and multiple-day chemotherapy regimens.

Clinical trial identification

ClinicalTrials.gov: NCT01594749; release: August 26, 2015

Legal entity responsible for the study

This work was supported by Merck & Co., Inc., Kenilworth, NJ

Funding

This work was supported by Merck & Co., Inc., Kenilworth, NJ

Disclosure

C. Weinstein, S. Green: Employee and stockholder of Merck & Co., Inc. K. Jordan: Honoraria for consultancy from Merck Sharp & Dohme (MSD), Merck & Co., Inc, Helsinn, and Pro-Strakan. E. Beckford-Brathwaite, W. Vallejos: Employee and stockholder of Merck & Co., Inc L.W. Liang: Employee of Merck & Co., Inc. S.J. Noga: Honoraria from Millenium and consultant or in an advisory role for Amgen and Millenium (now Takeda Oncology). B.L. Rapoport: Consultant or in an advisory role for and received payment for travel, accommodations, or expenses from MSD and Tesaro and also received payments for participation on speaker's bureau for MSD and Roche. All other authors have declared no conflicts of interest.