Randomized, Double-Blind, Phase III Study of Fosnetupitant Versus Fosaprepitant for Prevention of Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: CONSOLE

Abstract

Purpose: We evaluated the efficacy and safety of fosnetupitant (FosNTP) versus fosaprepitant (FosAPR) for preventing highly emetogenic chemotherapy-induced nausea and vomiting. This phase III study was the first head-to-head comparison between two different neurokinin-1 receptor antagonists in combination with palonosetron and dexamethasone.

Patients and methods: Patients scheduled to receive cisplatin-based chemotherapy were randomly assigned 1:1 to FosNTP 235 mg or FosAPR 150 mg in combination with palonosetron 0.75 mg and dexamethasone. The primary end point was overall (0-120 hours) complete response (CR; no emetic event and no rescue medication) rate, stratified by sex and age category, to show the noninferiority of FosNTP to FosAPR (noninferiority margin, -10% for the difference in the overall CR rate).

Results: Overall, 795 patients were randomly assigned, of whom 785 received the study drug (FosNTP [N = 392] v FosAPR [N = 393]) and were evaluated for efficacy and safety. The overall CR rate was 75.2% versus 71.0%, respectively (Mantel-Haenszel common risk difference, 4.1%; 95% CI, -2.1% to 10.3%), demonstrating noninferiority of FosNTP to FosAPR. The CR rates in the acute (0-24 hours), delayed (24-120 hours), and beyond delayed (120-168 hours) phases, and at 0-168 hours were 93.9% versus 92.6%, 76.8% versus 72.8%, 86.5% versus 81.4%, and 73.2% versus 66.9%, respectively. The incidence rates of treatment-related adverse events with FosNTP versus FosAPR were 22.2% versus 25.4%, whereas adverse events or treatment-related adverse events relevant to injection site reactions were 11.0% versus 20.6% (P < .001) and 0.3% versus 3.6% (P < .001), respectively.

Conclusion: FosNTP demonstrated noninferiority to FosAPR, with a favorable safety profile and lower risk for injection site reactions. Thus, FosNTP is valuable in the prophylaxis of acute, delayed, and beyond delayed chemotherapy-induced nausea and vomiting.

FIG 1.

CONSORT diagram (S-cycle). A total of 795 patients were enrolled in the S-cycle. The study drug was administered to 785 patients (FosNTP v FosAPR, n = 392 v n = 393, respectively), and all of them were evaluated for efficacy and safety. AE, adverse event; FAS, full analysis set; FosAPR, fosaprepitant; FosNTP, fosnetupitant; S-cycle, single chemotherapy cycle.

FIG 2.

CR rate by phase (S-cycle). The CR (no emetic event and no rescue medication) rates during the acute (0-24 hours), delayed (24-120 hours), and overall (0-120 hours) phases and at 0-168 hours and 120-168 hours in the full analysis set were calculated and their 95% CIs were estimated. The overall CR rate was stratified by sex and age category. CR, complete response; FosAPR, fosaprepitant; FosNTP, fosnetupitant; S-cycle, single chemotherapy cycle.

FIG 3.

TTF (S-cycle). The TTF (time to first emetic event or use of rescue medication) curve was estimated using the Kaplan-Meier method. FosAPR, fosaprepitant; FosNTP, fosnetupitant; HR, hazard ratio; S-cycle, single chemotherapy cycle; TTF, time to treatment failure.

FIG 4.

CINV incidence (S-cycle). CINV incidence (nausea and emetic events) was analyzed every 24 hours from the start of cisplatin administration to 168 hours. CINV, chemotherapy-induced nausea and vomiting; FosAPR, fosaprepitant; FosNTP, fosnetupitant; S-cycle, single chemotherapy cycle.