Systematic review of the efficacy and safety of neurokinin-1 receptor antagonists for chemotherapy-induced nausea and vomiting: identification of the relevant clinical trials

Abstract

Objectives: Chemotherapy-induced nausea and vomiting (CINV) is a common debilitating adverse event of chemotherapy. Antiemesis guidelines recommend combinations of neurokinin-1 receptor antagonists (NK-1 RAs) with dexamethasone and serotonin receptor antagonists (5-HT3RA) to prevent CINV in patients receiving highly emetogenic chemotherapy (HEC) and select patients receiving moderately emetogenic chemotherapy (MEC). This systematic review (SR) aimed to assess the availability of direct or indirect evidence for safety and efficacy of rolapitant versus other NK-1 RAs. Methods: An SR was conducted to identify RCTs comparing NK-1 RAs with any comparator via MEDLINE, Embase, Cochrane library electronic databases, meeting proceedings, clinical trails.gov, World Health Organization, clinical trials registry platform, FDA.gov and the European Union Clinical trials register websites. We followed prespecified inclusion and exclusion criteria, and screened eligible studies using the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We assessed the quality of the identified evidence using a checklist recommended by NICE for RCT quality assessment. Results: Overall, 29 publications on 29 RCTs (including one RCT and its extension) met the inclusion criteria (22 full publications, and 7 conference abstracts). Complete response (no vomiting and no use of rescue medication) in the overall, delayed, and acute phase, was a primary outcome in eleven, seven, and three RCTs, respectively. Rolapitant in combination with a 5-HT3RA and dexamethasone was compared with 5HT3RA and dexamethasone alone in three RCTs, in patients undergoing HEC or MEC. No RCT compared directly rolapitant with other NK-1 RAs for CINV management; however, 19 RCTs were potentially relevant for indirect comparison. Conclusions: Our review identified the RCTs evaluating NK1-RAs for CINV prevention in patients undergoing HEC or MEC. The lack of direct comparison between rolapitant and other NK-1 RAs suggests the need for a network metaanalysis indirectly comparing the effects of rolapitant with those of other NK-1 RAs.