Safety and Efficacy of Aprepitant as Mono and Combination Therapy for the Prevention of Emetogenic Chemotherapy-Induced Nausea and Vomiting

Post-Marketing Surveillance in China

Yunpeng Yang; Nong Yang; Lin Wu; Quchang Ouyang; Jian Fang; Jinfeng Li; Wangjun Liao; Kaican Cai; Jianjin Huang; Jin Li; Yiping Zhang; Xiaojia Wang; Helong Zhang; Nong Xu; Qiong Zhao; Xingsheng Hu; Wei Li; Wei Zhong; Diansheng Zhong; Gang Cheng; Sheng Ye; Meizuo Zhong; Dong Wang; Hui Liu; Jihua Zheng; Xiaojian Liu; Hong Xu; Li Zhang

Disclosures

Chin Clin Oncol. 2020;9(5):68 

In This Article

Abstract and Introduction

Abstract

Background: The goal of this study was to evaluate aprepitant usage in the context of routine clinical practice with dose/regimens at the discretion of prescribers for chemotherapy-induced nausea and vomiting (CINV) treatments.

Methods: In this single arm, multicenter prospective study 1,000 patients with solid malignancies were enrolled across 21 centers in China. The primary endpoint was the rate of adverse events (AEs), including drug related AEs and serious AEs (SAEs). Secondary efficacy endpoints included the proportion of patients achieving complete response (CR; no vomiting, no nausea, and no use of rescue medication) within 120 h after highly emetogenic chemotherapy, the rates of no nausea and no vomiting, as well as quality of life (QoL). Multivariable logistic regression analysis was carried out to determine factors associated with the overall (0–120 h), acute (0–24 h) and delayed (25–120 h) CR.

Results: Of the 1,000 highly emetogenic chemotherapy treated patients enrolled in the study ≥1 AE, ≥1 drug related AE, ≥1 SAE and drug related SAE rates in 998 patients were 45.9%, 2.5%, 4.0% and 0.1%, respectively. Approximately half of the patients (455/990, 46.0%) received aprepitant as part of a 3-drug anti-CINV regimen consistent with prescribing guidelines. The overall CR (0 to 120 h) for anti-emetic drug use was 41.0%, with an acute CR of 66.0% and a delayed CR of 46.5%. The rates of no vomiting and no nausea after solely aprepitant anti-emetic therapy from 0 to 120 h were 70.9% and 43.0%, for dual anti-emetic therapy 86.9% and 64.6%, and for triple therapy 86.4% and 69.5%, respectively. Multivariate regression analysis revealed that triple anti-emetic therapy (P=0.038), male gender (P<0.001) and a history of chemotherapy (P=0.016) were significantly associated with the overall acute CR.

Conclusions: Especially as a combination treatment, aprepitant is safe and efficient for preventing CINV in patients receiving highly emetogenic chemotherapy.

Introduction

Nausea and vomiting are common adverse events (AE) associated with cancer chemotherapy, affecting approximately 70% of treated patients, despite significant improvements in treatment options available for the management of cancer.[1,2] Chemotherapy-induced nausea and vomiting (CINV) has been found to negatively impact the patients' quality of life (QoL), leading to loss of appetite, general fatigue, constipation[3] and hospitalization.[4] However, CINV is preventable[5,6] and neurokinin-1 (NK-1) receptor antagonists as combination antiemetic therapy with a serotonin receptor (5HT3) antagonist and dexamethasone can be used to prevent CINV associated with moderate and highly emetogenic chemotherapy.[7]

Previous studies have shown that compared to moderate emetogenic chemotherapy,[8,9] patients treated with high emetogenic therapy were at a greater risk of overall and delayed CINV,[10,11] which may reach an incidence rate of >90% if suitable anti-emetic therapy is not prescribed.[12] Given the role of NK-1 receptors[13] in the induction of delayed nausea and vomiting, the European Society of Medical Oncology (ESMO), the Multinational Association of Support Care Cancer (MASCC) and National Comprehensive Cancer Network (NCCN) guidelines recommend administering a triple combination consisting of a 5HT3 receptor antagonist, dexamethasone and a NK-1 receptor antagonist for patients receiving highly emetogenic chemotherapy.[14,15]

Aprepitant is a NK-1 receptor antagonist commonly used for the prevention of CINV[16] and in combination with a 5HT3 receptor antagonist and dexamethasone has been shown to have potent anti-emetic activity in a pooled analysis of two phase III clinical trials.[17] In these studies, aprepitant demonstrated significant efficacy in the prevention of acute or delayed nausea and vomiting associated with highly or moderate emetogenic chemotherapy therapy.[17] In addition, in the aprepitant group, women had a greater overall complete response (CR) compared to men, which suggested the administration of aprepitant may be beneficial in preventing CINV in female patients receiving highly emetogenic chemotherapy.[17] A phase III trial revealed that aprepitant combined with ondansetron, with or without dexamethasone, may be an effective treatment regimen for the prevention of CINV in pediatric patients receiving highly or moderate emetogenic chemotherapy.[18]

It has also been reported, however, that aprepitant may influence the toxicity and the efficacy of concomitantly administered drugs, since a recent systematic review evaluated the possible pharmacokinetic drug interactions with aprepitant and fosaprepitant, and concluded that concurrent administration of aprepitant, ifosfamide, oxycodone, quetiapine, selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors and warfarin may lead to AEs including neurotoxicity, a decreased respiratory rate, somnolence, vomiting and prothrombin time/international normalized ratio changes.[19] A retrospective analysis of the NK-1 receptor antagonist, fosaprepitant, found that administration of fosaprepitant and anthracyclines through the same peripheral vein may cause a local reaction including swelling, extravasation and phlebitis at the infusion site.[20] However, other AEs related to interactions of aprepitant with co-medications are rarely reported.

In the present study, we carried out a multicenter, single arm, prospective clinical study in China to evaluate the safety and efficacy of aprepitant in Chinese patients receiving highly emetogenic chemotherapy for the treatment of solid malignancies in the context of routine clinical practices. We also analyzed the factors associated with CR and assessed potential anti-emetic drug interactions associated with concomitant therapy. We present the following article in accordance with the TREND reporting checklist (available at http://dx.doi.org/10.21037/cco-20-160).

processing....