Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: results of a randomized, double-blind phase III trial.

Abstract

BACKGROUND:

To establish the role of antiemetic therapy with neurokinin-1 (NK1) receptor antagonists (RAs) in nonanthracycline and cyclophosphamide (AC)-based moderately emetogenic chemotherapy (MEC) regimens, this study evaluated single-dose intravenous (i.v.) fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) associated with non-AC MEC.

PATIENTS AND METHODS:

In this international, phase III, double-blind trial, adult cancer subjects scheduled to receive ≥1 non-AC MEC on day 1 were randomized to a regimen comprising single-dose i.v. fosaprepitant 150 mg or placebo along with ondansetron and dexamethasone on day 1; control regimen recipients received ondansetron on days 2 and 3. Primary end points were the proportion of subjects achieving a complete response (CR; no vomiting and no use of rescue medication) in the delayed phase (25-120 h after MEC initiation) and safety. Secondary end points included CR in the overall and acute phases (0-120 and 0-24 h after MEC initiation, respectively) and no vomiting in the overall phase. Nausea and the Functional Living Index-Emesis were assessed as exploratory end points.

RESULTS:

The fosaprepitant regimen improved CR significantly in the delayed (78.9% versus 68.5%; P < 0.001) and overall (77.1% versus 66.9%; P < 0.001) phases, but not in the acute phase (93.2% versus 91.0%; P = 0.184), versus control. In the overall phase, the proportion of subjects with no vomiting (82.7% versus 72.9%; P < 0.001) and no significant nausea (83.2% versus 77.9%; P = 0.030) was also significantly improved with the fosaprepitant regimen. The fosaprepitant regimen was generally well tolerated.

CONCLUSION:

Single-dose fosaprepitant added to a 5-HT3 RA and dexamethasone was well tolerated and demonstrated superior control of CINV (primary end point achieved) associated with non-AC MEC. This is the first study to evaluate NK1 RA therapy as an i.v. formulation in a well-defined non-AC MEC population.

CLINICALTRIALSGOV:

NCT01594749 (https://clinicaltrials.gov/ct2/show/NCT01594749).

• Authors: C Weinstein, K Jordan, S A Green, E Camacho, S Khanani, E Beckford-Brathwaite, W Vallejos, L W Liang, S J Noga, B L Rapoport
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 27 Issue 1 Pg. 172-8 (Jan 2016) ISSN: 1569-8041 [Electronic] England
• PMID: 26449391 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Chemical References

• Antiemetics
• Antineoplastic Agents
• Morpholines
• fosaprepitant

Topics

• Antiemetics (therapeutic use)
• Antineoplastic Agents (adverse effects, therapeutic use)
• Double-Blind Method
• Female
• Humans
• Lung Neoplasms (drug therapy)
• Male
• Middle Aged
• Morpholines (therapeutic use)
• Nausea (chemically induced, prevention & control)
• Treatment Outcome
• Vomiting (chemically induced, prevention & control)