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Study of rolapitant, a novel, long-acting, NK-1 receptor antagonist, for the prevention of chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC)

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Abstract

Purpose

Rolapitant is a novel, long-acting neurokinin-1 (NK-1) receptor antagonist. This study evaluated the safety and efficacy of four different doses of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC).

Methods

This randomized, double-blind, active-controlled, global study was conducted in patients receiving cisplatin-based chemotherapy ≥70 mg/m2. Patients received a 9, 22.5, 90, or 180 mg oral dose of rolapitant or placebo with ondansetron and dexamethasone on day 1 of chemotherapy. The primary end point was complete response (CR; no emesis and no use of rescue medication) in the overall (0 to 120 h) phase of cycle 1. Other assessments were CR in delayed (24–120 h) and acute (0–24 h) phases, no emesis, no significant nausea, and no nausea.

Results

Four hundred fifty-four patients were randomized. All doses of rolapitant improved CR with the greatest benefit observed with rolapitant 180 mg vs. active control in the overall phase (62.5 and 46.7 %, p = 0.032) and in the acute (87.6 vs. 66.7 %, p = 0.001) and delayed (63.6 vs. 48.9 %, p = 0.045) phases. Rates for no emesis and no significant nausea were significantly (p < 0.05) higher with rolapitant 180 mg vs. active control in the overall, acute, and delayed phases. Treatment-related adverse events were largely considered related to the chemotherapy and included constipation, headache, fatigue, and dizziness which were mostly mild or moderate and were similar across treatment groups.

Conclusion

All doses of rolapitant were well tolerated and showed greater CR rates than active control. Rolapitant 180 mg demonstrated significant clinical efficacy for preventing CINV in the overall, delayed, and acute phases for patients receiving HEC.

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Acknowledgments

Schering-Plough Corporation conducted the study, and TESARO, Inc. is reporting the results. The authors would like to acknowledge the editorial assistance of Richard S. Perry, PharmD, in the preparation of this manuscript, which was supported by TESARO Inc., Waltham, MA, and the help provided by Hajira B. Koeller, PhD, from TESARO Inc. in analyzing the data.

Authors’ contributions

All authors critically reviewed drafts of the manuscript, and all approved submission of the manuscript for publication. DC and LF were involved in the conduct of the study. BR, DC, LF, SA, and AP were involved in interpretation of the study results. SA performed the statistical analysis. YW was involved in the interpretation and writing of the manuscript.

Conflict of interest

Dr. Rapoport had full access to all of the primary data from this study and agrees to allow the journal to review the data, if requested. Dr. Rapoport received funding to conduct this research from Schering-Plough Corporation and currently serves as a consultant/advisor for TESARO, Inc.

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Authors and Affiliations

  1. The Medical Oncology Centre of Rosebank, 129 Oxford Road, Corner Northwold, Saxonwold, Johannesburg, South Africa

    Bernardo Rapoport

  2. The University of Hong Kong, Pok Fu Lam, Hong Kong

    Daniel Chua

  3. TESARO Inc, Waltham, MA, USA

    Allen Poma, Sujata Arora & Yan Wang

  4. Centro Oncologico de Rosario, Santa Fe, Argentina

    Luis Enrique Fein

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  1. Bernardo Rapoport
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Correspondence to Bernardo Rapoport.

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Rapoport, B., Chua, D., Poma, A. et al. Study of rolapitant, a novel, long-acting, NK-1 receptor antagonist, for the prevention of chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC). Support Care Cancer 23, 3281–3288 (2015). https://doi.org/10.1007/s00520-015-2738-1

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