Efficacy and safety of aprepitant for the prevention of chemotherapy-induced nausea and vomiting during the first cycle of moderately emetogenic chemotherapy in Korean patients with a broad range of tumor types
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This study evaluated the efficacy and safety of a 3-day aprepitant regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) during the first cycle of non-anthracycline plus cyclophosphamide (AC)-based moderately emetogenic chemotherapy (MEC) based on government guidelines in Korean patients.
This multicenter, randomized, double-blind, phase IV trial (NCT01636947) enrolled adult South Korean patients with a broad range of tumor types who were scheduled to receive a single dose of ≥1 MEC agent. Patients were randomized to a 3-day regimen of aprepitant (aprepitant regimen) or placebo (control regimen) on top of ondansetron plus dexamethasone. The primary and key secondary efficacy endpoints were the proportions of subjects who achieved no vomiting and complete response (CR) during the overall phase.
Of the 494 randomized subjects, 480 were included in the modified intent-to-treat population. Response rates for no vomiting and CR in the overall phase were numerically higher for the aprepitant regimen compared with the control regimen groups, but failed to reach statistical significance (no vomiting 77.2 vs 72.0%; p = 0.191; CR 73.4 vs 70.4%; p = 0.458). Both the aprepitant and control regimens were generally well tolerated.
A 3-day aprepitant regimen was numerically better but not statistically superior to a control regimen with respect to the achievement of no vomiting or CR during the overall phase in a non-AC MEC Korean population based on government reimbursement guidelines.
KeywordsAprepitant Neurokinin-1 receptor antagonists Moderately emetogenic chemotherapy, Chemotherapy-induced nausea and vomiting
We would like to thank DreamCIS, Inc., for providing clinical research services for this study. Medical writing and editorial assistance was provided by Maxwell Chang and Traci Stuve of ApotheCom, Yardley, PA, with funding provided by Merck & Co., Inc., Kenilworth, NJ.
Jeong Eun Kim, Joung-Soon Jang, and Kyung Wan Min are responsible for the work described in this paper. All authors were involved in at least one of the following: conception, design, acquisition, analysis, statistical analysis, interpretation of data and drafting the manuscript and/or revising the manuscript for important intellectual content. Jae-Weon Kim, Myong Choel Lim, Kil Yeon Lee, and Sun Jin Sym were also responsible for provision of study materials or patients. All authors provided final approval of the version to be published.
Compliance with ethical standards
Conflict of interest
Hun Jung, Cho Eun Kim, and Kyung Wan Min are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., who may potentially own stock and/or hold stock options in the company. The remainder of the authors has nothing to disclose.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
- 5.National Comprehensive Cancer Network, Inc. NCCN (2014) Clinical Practice Guidelines in Oncology. Antiemesis. Version 1.2014. National Comprehensive Cancer Network Web siteGoogle Scholar
- 7.Roila F, Herrstedt J, Aapro M, Gralla RJ, Einhorn LH, Ballatori E, Bria E, Clark-Snow RA, Espersen BT, Feyer P, Grunberg SM, Hesketh PJ, Jordan K, Kris MG, Maranzano E, Molassiotis A, Morrow G, Olver I, Rapoport BL, Rittenberg C, Saito M, Tonato M, Warr D (2010) Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol 21(suppl 5):v232–v243CrossRefPubMedGoogle Scholar
- 8.Warr DG, Hesketh PJ, Gralla RJ, Muss HB, Herrstedt J, Eisenberg PD, Raftopoulos H, Grunberg SM, Gabriel M, Rodgers A, Bohidar N, Klinger G, Hustad CM, Horgan KJ, Skobieranda F (2005) Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol 23:2822–2830CrossRefPubMedGoogle Scholar
- 9.Rapoport BL, Jordan K, Boice JA, Taylor A, Brown C, Hardwick JS, Carides A, Webb T, Schmoll HJ (2010) Aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with a broad range of moderately emetogenic chemotherapies and tumor types: a randomized, double-blind study. Support Care Cancer 18:423–431CrossRefPubMedGoogle Scholar
- 10.Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, Julie MG, Eldridge K, Hipple A, Evans JK, Horgan KJ, Lawson F (2003) Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Results from a randomized, double-blind, placebo-controlled trial in Latin America. Cancer 97:3090–3098CrossRefPubMedGoogle Scholar
- 11.Hesketh PJ, Grunberg SM, Gralla RJ, Warr DG, Roila F, de W R, Chawla SP, Carides AD, Ianus J, Elmer ME, Evans JK, Beck K, Reines S, Horgan KJ (2003) The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin—the aprepitant protocol 052 study group. J Clin Oncol 21:4112–4119CrossRefPubMedGoogle Scholar
- 12.Gralla RJ, De Wit R, Herrstedt J, Carides AD, Ianus J, Guoguang-Ma J, Evans JK, Horgan KJ (2005) Antiemetic efficacy of the neurokinin-1 antagonist, aprepitant, plus a 5HT3 antagonist and a corticosteroid in patients receiving anthracyclines or cyclophosphamide in addition to high-dose cisplatin: analysis of combined data from two phase III randomized clinical trials. Cancer 104:864–868CrossRefPubMedGoogle Scholar
- 13.Roila F, Herrstedt J, Aapro M, et al. for the ESMO/MASCC Guidelines Working Group (2013) MASCC/ESMO antiemetic guideline 2013. Multinational Association of Supportive Care in Cancer. http://www.mascc.org/antiemetic-guidelines. Accessed February 9, 2016.
- 15.Basch E, Prestrud AA, Hesketh PJ, Kris MG, Feyer PC, Somerfield MR, Chesney M, Clark-Snow RA, Flaherty AM, Freundlich B, Morrow G, Rao KV, Schwartz RN, Lyman GH (2011) Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 29:4189–4198CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Health Insurance Review & Assessment Services (2015) Oncology medicine reimbursement guideline.Google Scholar
- 18.Hickok JT, Roscoe JA, Morrow GR, Bole CW, Zhao H, Hoelzer KL, Dakhil SR, Moore T, Fitch TR (2005) 5-Hydroxytryptamine-receptor antagonists versus prochlorperazine for control of delayed nausea caused by doxorubicin: a URCC CCOP randomised controlled trial. Lancet Oncol 6:765–772CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Gralla RJ, Rapoport BL, Jordan K, Street JC, Carides A (2010) Assessing the magnitude of antiemetic benefit with the addition of the NK1 receptor antagonist (NK1) aprepitant for all platinum agents: analysis of 1,872 patients (pts) in prospective randomized clinical phase III trials (RCTs). J Clin Oncol 28(15 suppl):9057Google Scholar
- 22.Tanioka M, Kitao A, Matsumoto K, Shibata N, Yamaguchi S, Fujiwara K, Minami H, Katakami N, Morita S, Negoro S (2013) A randomised, placebo-controlled, double-blind study of aprepitant in nondrinking women younger than 70 years receiving moderately emetogenic chemotherapy. Br J Cancer 109:859–865CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Ito Y, Karayama M, Inui N, Kuroishi S, Nakano H, Nakamura Y, Yokomura K, Toyoshima M, Shirai T, Masuda M, Yamada T, Yasuda K, Hayakawa H, Suda T, Chida K (2014) Aprepitant in patients with advanced non-small-cell lung cancer receiving carboplatin-based chemotherapy. Lung Cancer 84:259–264CrossRefPubMedGoogle Scholar