Fosnetupitant demonstrated non-inferiority and a favorable safety profile vs fosaprepitant for chemotherapy-induced nausea and vomiting.
Prophylactic treatment with fosnetupitant (FosNTP) for chemotherapy-induced nausea and vomiting resulted in favorable safety, a lower risk of injection site reactions, and appeared to be noninferiority to fosaprepitant (FosAPR), according to results from the phase 3 CONSOLE trial that were published in the Journal of Clinical Oncology.
FosNTP yielded a complete response (CR) rate was 75.2% vs 71.0% for those with FosAPR (Mantel-Haenszel common risk difference, 4.1%; 95% CI, –2.1% to 10.3%). The CR rate in the acute group (0-24 hours) was 93.9% vs 92.6%, 76.8% vs 72.8% in the delayed group (24-120 hours), 86.5% vs 81.4% in the beyond delayed group (120-168 hours), and 73.2% vs 66.9% for 0 to 168 hours when treated with FosNTP and FosAPR, respectively. The hazard ratio for time to treatment failure was 0.789 (95% CI, 0.61-1.021; P = .071).
A total of 795 patients were enrolled on the study and were randomized. Additionally, 785 patients received the study treatment and 779 completed the cycle. In the FosNTP group, 16.3% of patients required rescue medication during the efficacy observation period, compared with 17.8% in the FosAPR group.
In a single chemotherapy cycle, patients were given 235 mg of FosNTP, 0.75 mg of palonosetron, and 9.9 mg of dexamethasone which were infused for 30 minutes and began 1 hour prior to cisplatin infusion. FosAPR was infused at 150 mg for 30 minutes starting 1 hour before cisplatin. Additionally, 0.75 mg of palonosetron and 9.9 mg of dexamethasone were infused separately due to the possible risk of incompatibility between FosAPR and palonosetron. This was started 30 minutes before FosAPR was administered or immediately after depending on the study site.
Investigators observed intergroup similarity between those who developed adverse effects (AEs; 99.5% vs 99.0%), treatment-related AEs (TRAEs; 22.2% vs 25.4%), and TRAEs that were grade 3 or higher (2.6% vs 3.1%) in the FosNTP and FosAPR groups, respectively. Between both groups, 1.0% or less of patients developed grade 3 or higher TRAEs. The most common TRAEs in 5% or more of patients included constipation (11.2% vs 13.7%), and hiccups (4.8% vs 7.1%), in the FosNTP and FosAPR groups, respectively.
Patients in the FosNTP group had a significantly lower proportion of patients who experienced AEs or TRAEs related to injection site reactions (11.0% vs 20.6%; P <.001; 0.3% vs 3.6%; P <.001) compared with the FosAPR arm. No patient experienced TRAEs or AEs that led to death in the FosNTP group. Serious TRAEs in the FosAPR group included ischemic colitis and erythema multiforme.
A total of 129 patients enrolled, 126 of whom received treatment with multiple chemotherapy cycles. This included 65 patients in the FosNTP group in the single cycle and 61 in the FosAPR group. During course 3, the only TRAEs that was reported in 5% of patients or more was hiccups (5.9%). During course 4, 1 patient experienced a TRAE related to an injection site reaction. Patients in this group had about the same CR rate as in the single chemotherapy cycle, and efficacy was maintained throughout.
Hata A, Okamoto I, Inui N, et al. Randomized, double-blind, phase III study of fosnetupitant versus fosaprepitant for prevention of highly emetogenic chemotherapy-induced nausea and vomiting: CONSOLE. J Clin Oncol. 2022;40(2):180-188. doi:10.1200/JCO.21.01315