Efficacy of neurokinin-1 receptor antagonists in the prevention of chemotherapy-induced nausea and vomiting in patients receiving carboplatin-based chemotherapy: A systematic review and meta-analysis

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Abstract

According to current ESMO – MASCC guidelines, a combination of a neurokinin-1 receptor antagonist (NK1RA), dexamethasone and a 5-HT3 receptor antagonist (5-HT3RA) is recommended to prevent carboplatin-induced emesis, albeit with moderate level of confidence and not unanimous consensus. We performed a meta-analysis of randomized trials (RCTs) comparing NK1RA + dexamethasone + 5-HT3RA vs. dexamethasone + 5-HT3RA in patients receiving the first cycle of carboplatin-based chemotherapy. Primary outcome was complete response (CR), defined as no emesis and no use of rescue medication. 9 trials were eligible, and data of CR were available from 8 trials (1598 patients). Addition of NK1RA improves CR in all phases: acute phase, 94.5% vs. 90.1%; delayed phase, 76.4% vs. 61.7%; overall period, 75.3% vs. 60.4%. There was no significant heterogeneity among trials. In patients receiving carboplatin-based chemotherapy, the addition of NK1RA to dexamethasone and 5-HT3RA is associated with a statistically significant and clinically relevant improvement in CR.

Introduction

Nausea and vomiting are common adverse events in cancer patients receiving chemotherapy (Laszlo, 1983; Navari and Aapro, 2016). Chemotherapy-induced nausea and vomiting (CINV) can significantly affect health-related quality of life (QoL) of cancer patients and can impair compliance with treatments (Ballatori and Roila, 2003; Ballatori et al., 2007). For these reasons, a correct management of CINV is essential. According to guidelines, all antineoplastic agents are classified, based on their emetogenic potential, on a 4-group scale: high (emetic risk >90%), moderate (30%–90%), low (10%–30%), and minimal (<10%) emetogenic chemotherapy (Ballatori et al., 2007). For each category, guidelines recommend different strategies to prevent CINV: a triple drug strategy with 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists (RAs) plus dexamethasone plus Neurokinin-1 (NK-1) RAs is currently recommended in highly emetogenic chemotherapy (HEC) (such as cisplatin-based treatment or combination of anthracyclines and cyclophosphamide in breast cancer patients) to prevent acute and delayed nausea and vomiting (Roila et al., 2016; Moher et al., 2009). In patients receiving moderately emetogenic chemotherapy (MEC) such as oxaliplatin and irinotecan, only 5-HT3RA and dexamethasone are recommended. Instead, for carboplatin, the latest ESMO-MASCC guidelines recommend a different prophylaxis compared to other MEC, consisting in a triple combination of 5-HT3RA plus dexamethasone plus NK-1RA (Roila et al., 2016). However, the level of confidence was moderate, and the consensus reached among panelists was not unanimous.

To better define the value of NK-1RAs addition in the prevention of emesis for patients receiving carboplatin-based chemotherapy, we conducted a systematic review and a literature-based meta-analysis of all randomized trials (RCTs) published to date.

Section snippets

Methods

This systematic review and meta-analysis was conducted and reported according to PRISMA guidelines (Herrstedt et al., 2011). Full protocol of the review is available on request from the corresponding author.

The systematic review was performed in January 2017 and updated in June 2017, in order to identify all RCTs comparing NK1RA + dexamethasone + 5-HT3RA vs. dexamethasone + 5-HT3RA in patients receiving the first cycle of carboplatin-based chemotherapy. PubMed search was based on the following

Results

Out of 180 records, 173 were excluded and 7 trials were identified as potentially eligible (Fig. 1) (Tanioka et al., 2013; Ito et al., 2014; Kusagaya et al., 2015; Kaushal et al., 2015; Maehara et al., 2015; Yahata et al., 2016; Hesketh et al., 2016). In addition, 2 trials were found in the proceedings of meetings (Weinstein et al., 2016; Gralla et al., 2010), for a total of 9 trials potentially eligible. More specifically, 7 trials tested the role of aprepitant, 1 fosaprepitant and 1

Discussion

In this meta-analysis, we collected the results of all RCTs comparing antiemetic prophylaxis based on the combination of 5-HT3RA plus dexamethasone with the same combination implemented with a NK1RA, in patients undergoing carboplatin-based chemotherapy. Through the comparison of complete response rates (defined as no episodes of emesis and no need for rescue medications), we demonstrated that the addition of a NK1RA significantly increases the rate of success in the control of CINV after the

Funding

None.

Conflicts of interest statement

Massimo Di Maio had roles as advisor, and speaker’s fee for Merck Sharp & Dohme, AstraZeneca, Bayer, Janssen, Bristol Myers Squibb, and Eli Lilly. Emilio Bria had roles as advisor, and speakers’ fee for Merck Sharp & Dohme, AstraZeneca, Celgene, Pfizer, Eli-Lilly, Bristol Myers Squibb, and Novartis. All remaining authors declared no conflicts of interest.

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