Efficacy and safety of multiple doses of NEPA without dexamethasone in preventing nausea and vomiting induced by multiple-day and high-dose chemotherapy in patients with non-Hodgkin\u2019s lymphoma undergoing autologous hematopoietic stem cell transplantation: a phase IIa, multicenter study

Nicola Di Renzo,Rosanna Scimè,Federico Verde ,Domenico Pastore,Luca Cupelli,Attilio Guarini,Anna Rita Messa,Patrizia Chiusolo,Andrea Mengarelli,Patrizio Mazza,Valentina Bozzoli,Fabio Benedetti,Maurizio Musso,Erminio Bonizzoni,Vera Capria,Alessandra Cupri,Paolo Codega,Clara De Risi,Tommasina Perrone,Giorgina Specchia

doi:10.1038/s41409-020-0909-2

Abstract

Despite the availability of several antiemetics, clinical findings show that control of chemotherapy-induced nausea and vomiting (CINV) continues to be a serious concern for hematological patients, mainly for those receiving multiple-day (MD) and high-dose (HD) chemotherapy (CT). For CINV prophylaxis, 5-hydroxytryptamine type-3 receptor antagonists (5HT3-RAs) and neurokinin 1 receptor antagonists (NK1-RAs) are usually administered together with dexamethasone, which may increase the risk of serious infections in patients undergoing myeloablative treatment. The rationale of this multicenter, open-label and phase IIa study was to explore the efficacy of multiple doses of NEPA (netupitant/palonosetron) given as an every-other-day regimen without dexamethasone in preventing CINV in patients with relapsed-refractory aggressive non-Hodgkin’s lymphoma (R/R-NHL), eligible for autologous stem cell transplantation (ASCT) and treated with MD-HD-CT. Seventy patients participated to the study. According to the adopted Fleming one-stage design, the primary endpoint of this study was achieved. The CR values were 87.1% (primary endpoint, overall phase: days 1–8), 88.6% (acute phase: days 1–6), and 98.6% (delayed phase: days 7–8), while complete control (CR with no more than mild nausea) was 85.7% (overall phase), 88.6% (acute phase), and 95.7% (delayed phase). Moderate and severe episodes of nausea were reported by less than 10% of patients in the overall phase and less than 5% in both the acute and delayed phases. Regarding safety, NEPA was well tolerated with only one adverse event (constipation) evaluated as possibly related to NEPA administration. In conclusion, our study demonstrated that multiple alternate dosing of NEPA without the addition of dexamethasone is highly effective for preventing nausea and vomiting in this difficult setting, with a good tolerability profile.

Highlights

Cancer chemotherapy (CT) may induce nausea and vomiting (CINV) and uncontrolled chemotherapy-induced nausea and vomiting (CINV) can be detrimental for the patient, affecting the quality of life by causing dehydration, electrolyte imbalance, and malnutrition and potentially altering patient adherence to life-savingExtended author information available on the last page of the article treatments [1]
Among the antiemetics available for CINV prophylaxis, the most effective drugs are inhibitors of two receptors involved in the control of nausea and vomiting: 5-hydroxytryptamine type-3 receptor antagonists (5HT3-RAs) and neurokinin
NEPA is a fixed dose combination antiemetic that combines palonosetron, a second-generation 5HT3-RA, with a prolonged half-life and a higher receptor affinity compared with other first generation 5HT3-RAs [9,10,11,12], with netupitant a novel, highly selective neurokinin 1 receptor antagonists (NK1-RAs) [13, 14]

Summary

Introduction

Cancer chemotherapy (CT) may induce nausea and vomiting (CINV) and uncontrolled CINV can be detrimental for the patient, affecting the quality of life by causing dehydration, electrolyte imbalance, and malnutrition and potentially altering patient adherence to life-savingExtended author information available on the last page of the article treatments [1]. NEPA is a fixed dose combination antiemetic that combines palonosetron, a second-generation 5HT3-RA, with a prolonged half-life and a higher receptor affinity compared with other first generation 5HT3-RAs [9,10,11,12], with netupitant a novel, highly selective NK1-RA [13, 14]. Both molecules have an extended half-life (palonosetron: 40 h; netupitant: 90 h) and their combination makes a single oral administration sufficient to cover the acute and the delayed phase of CINV induced by a single day CT [15,16,17]. NEPA plus dexamethasone showed superiority over oral palonosetron plus dexamethasone for all key efficacy endpoints during both the delayed and the overall (5 days) phases following either cisplatin-based HEC or anthracycline/cyclophosphamide CT [15, 16]

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Conclusion