Meta-Analysis of Trials Comparing Standard Antiemetic Treatment (SAT) Versus Aprepitant-Containing Anti-Emetic Regimens (ACAR) for Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV)

Abstract

Introduction: Aprepitant is a neurokinin-1 (NK-1) receptor antagonist which blocks the emetic effects of substance P. Various randomized controlled trials (RCTs) have shown improved outcomes with addition of aprepitant to standard antiemetic treatment (SAT) for preventing CINV in adults. We conducted a systematic review and meta-analysis to study the overall impact of aprepitant in CINV prevention. Methods: We searched Pubmed and Ovid databases, and American Society of Clinical Oncology meetings proceedings for RCTs that studied aprepitant combination with SAT for prevention of CINV in adult cancer patients. Major study end-points were complete response to treatment (CR; defined as no emesis and no use of rescue medications) in the overall phase (OP; 0-120 hours of chemotherapy), acute phase (AP; 0-24 hours) and delayed phase (DP; 24-120 hours). Additionally, we assessed control of nausea in each phase, use of rescue medications in each phase, and toxicity profile (TP). Stouffer’s Z-score method was used to test for the overall effect. Results: Sixteen trials (5,547 patients) were included. Eleven trials (3,314 patients) involved highly emetogenic chemotherapy (HEC) and 5 trials (2,233 patients) involved moderately emetogenic chemotherapy (MEC). ACAR increased the CR rate in OP from 47% to 63% (odds ratio [OR]=0.52; confidence interval [CI]=0.46 to 0.58; p<0.001). CR rate improved from 73% to 81% in AP (p<0.01), and 51% to 66% in DP (p<0.001). Significant increase in control of nausea was seen in DP (p=0.03), but not in OP or AP. Decrease in use of rescue medications was significant in OP (p=0.02) and DP (p=0.03), but not in AP. Frequency of various toxicities was statistically similar in both groups, except slightly higher incidence of fatigue (p=0.02) and hiccups (p<0.001), and lower incidence of neutropenia (p=0.02) in ACAR. Conclusion: ACAR is effective in CINV due to both HEC and MEC treatments. ACAR improves the control of emesis in all phases, whereas improvement in nausea in seen in delayed phase only. With the exception of more fatigue and hiccups, and lesser neutropenia, overall TP of ACAR is similar to SAT. Addition of aprepitant to the anti-emetic therapy should be strongly considered by oncologists, especially while administering HEC. Future research avenues include exploring the use of other NK-1 receptor antagonists in prevention of CINV.