Chemotherapy-induced nausea and vomiting (CINV) often develops after chemotherapy use for the treatment of malignant tumors. A team of researchers in Japan compared the efficacy and safety of fosnetupitant (FosNTP) with fosaprepitant (FosAPR), another neurokinin-1 receptor antagonist, in preventing CINV. The results of their randomized, double-blind, phase III study were published in the Journal of Clinical Oncology.

Guidelines recommend proactive preventive measures when patients are receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy. Japanese guidelines recommend a triplet therapy consisting of a neurokinin-1 (NK1) receptor antagonist (RA), a serotonin (5-HT3) RA, and dexamethasone.

The researchers sought to determine which is more effective: FosAPR, an injectable prodrug of aprepitant, or FosNTP, an injectable phosphorylated prodrug of netupitant. For this study, 785 patients scheduled to receive cisplatin-based chemotherapy were randomly assigned to a regimen of FosNTP 235 mg (392 patients) or FosAPR 150 mg (393 patients) in tandem with palonosetron 0.75 mg and dexamethasone. Overall complete response, defined as no emetic event or rescue medication needed, was the primary endpoint.

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The head-to-head comparison demonstrated that FosNTP works well and is noninferior to FosAPR. Complete response rates were 75.2% and 71.0% for FosNTP and FosAPR, respectively.

Incidence rate of treatment-related adverse events were 22.2% with FosNTP and 25.4% with FosAPR. However, the proportion of patients who experienced injection site reactions was significantly lower with FosNTP (11.0% vs 20.6%).

Japanese guidelines recommend a triplet therapy; however, the American Society of Clinical Oncology and the National Comprehensive Cancer Center recommend a quartet therapy. The researchers noted that “the lack of comparison with a quartet therapy including olanzapine” was a limitation.

This study demonstrated that FosNTP was noninferior to FosAPR in combination with palonosetron and dexamethasone in patients receiving HEC. The significantly lower incidence of injection site reactions also confirm the good safety profile of FosNTP, the researchers concluded.

Disclosure: Multiple authors declared an affiliation with a biotech, pharmaceutical, and/or device company. Please see the original reference for a full list of authors’ disclosures.


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. Published online November 18, 2021. doi:10.1200/JCO.21.01315