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Defining the efficacy of neurokinin-1 receptor antagonists in controlling chemotherapy-induced nausea and vomiting in different emetogenic settings—a meta-analysis

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Abstract

Purpose

This meta-analysis was performed to evaluate the efficacy of neurokinin-1 receptor antagonists (NK1RAs) for the prevention of chemotherapy-induced nausea and vomiting (CINV) across different categories of chemotherapeutic emetogenicity.

Methods

A systematic review of MEDLINE (via PubMed) and OVID databases, plus major oncology conferences, identified randomized, controlled trials evaluating NK1RAs in combination with a 5-HT3 RA plus a glucocorticoid for management of CINV. Efficacy end points were no emesis, no nausea, and complete response (CR) rates. Data were analyzed using a random effects model.

Results

Twenty-three trials (N = 11,814) were identified. Based on absolute differences (AD) for no emesis (21 %), no nausea (8 %), CR (16 %), and odd ratios (OR) of 2.62, 1.43, and 2.16, respectively, NK1RA regimens provided better CINV protection versus control groups (all p < 0.00001) in patients receiving cisplatin-based highly emetogenic chemotherapy (HEC). In patients receiving anthracycline/cyclophosphamide (AC)-based HEC, respective ADs and ORs were 14, 4, and 11 % and 1.97 (p < 0.0001), 1.17 (p = 0.04), and 1.62 (p < 0.00001). In patients receiving moderately emetogenic chemotherapy (3 trials), no statistically significant benefit of NK1RAs was found; however, positive trends were detected for CR and no emesis. NK1RAs were effective for CINV prevention in a small number of studies using high-dose chemotherapy as conditioning prior to stem cell transplant and cisplatin-based multiple-day chemotherapy (MDC).

Conclusions

This meta-analysis demonstrated the efficacy of NK1RA in preventing vomiting in patients receiving HEC (including AC), with smaller effects on prevention of nausea. Efficacy is also seen with high-dose chemotherapy and cisplatin-based MDC.

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Acknowledgments

Editorial and medical writing support was provided by Andrea Bothwell and Traci Stuve of ApotheCom, with funding provided by Merck & Co., Inc. Statistical support was funded by Merck & Co., Inc.

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Authors and Affiliations

  1. Department of Internal Medicine IV, Hematology/Oncology, Martin-Luther- University Halle-Wittenberg, Ernst-Grube-Strasse 40, 06120, Halle, Germany

    Karin Jordan

  2. Princess Margaret Hospital, 610 University Avenue, Toronto, M5G 2M9, Canada

    David G. Warr

  3. WiSP Wissenschaftlicher Service Pharma GmbH, Karl-Benz-Strasse 1, D-40764, Langenfeld, Germany

    Axel Hinke

  4. Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ, 07033, USA

    Linda Sun

  5. Department of Hematology Oncology, Lahey Hospital & Medical Center, 41 Mall Road, Burlington, MA, 01805, USA

    Paul J. Hesketh

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  1. Karin Jordan
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Correspondence to Karin Jordan.

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Authors’ disclosures of potential conflicts of interest

Karin Jordan has received honoraria from and has served on advisory boards for Merck & Co., Inc., and Helsinn. Axel Hinke has received research funding from Merck & Co., Inc. Linda Sun is an employee and stockholder of Merck & Co., Inc. David Warr has served on advisory boards for and has received research funding and honoraria from Merck & Co., Inc. Paul Hesketh has served on advisory boards for Helsinn.

Author contributions

K. Jordan, A. Hinke, P. Hesketh, and D. Warr were involved in the conception and design of the study, and K. Jordan and A. Hinke were responsible for data collection and assembly. The statistical analysis, performed by A. Hinke, was checked by and discussed with L. Sun. All authors provided input on data analysis and interpretation, and all authors reviewed and provided input on the outline and manuscript drafts and provided final approval for manuscript submission.

Financial support

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

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Jordan, K., Warr, D.G., Hinke, A. et al. Defining the efficacy of neurokinin-1 receptor antagonists in controlling chemotherapy-induced nausea and vomiting in different emetogenic settings—a meta-analysis. Support Care Cancer 24, 1941–1954 (2016). https://doi.org/10.1007/s00520-015-2990-4

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