In a Japanese phase III noninferiority trial (CONSOLE) reported in the Journal of Clinical Oncology, Hata et al found that fosnetupitant was noninferior to fosaprepitant in preventing nausea and vomiting in patients receiving highly emetogenic chemotherapy (both in combination with palonosetron and dexamethasone), and was also associated with a lower incidence of injection site reactions.

Study Details

In the double-blind multicenter trial, 785 patients scheduled to receive cisplatin-based chemotherapy were randomly assigned between February 2019 and March 2020 to receive infusions of fosnetupitant at 235 mg (n = 392) or fosaprepitant at 150 mg (n = 393) in combination with palonosetron at 0.75 mg and dexamethasone at 9.9 mg starting 1 hour prior to cisplatin administration. Most patients (90% and 87%) had lung cancer. The primary endpoint was overall (0–120 hours) complete response, defined as no emetic event and no rescue medication. The noninferiority margin for fosnetupitant vs fosaprepitant was a -10% difference in overall complete response rate.

Complete Response Rates

The overall complete response rate was 75.2% in the fosnetupitant group vs 71.0% in the fosaprepitant group (risk difference = 4.1%, 95% confidence interval = –2.1% to 10.3%), demonstrating noninferiority of fosnetupitant.

Complete response rates were 93.9% vs 92.6% in the acute phase (0–24 hours), 76.8% vs 72.8% in the delayed phase (24–120 hours), 86.5% vs 81.4% in the beyond delayed phase (120–168 hours), and 73.2% vs 66.9% over 0–168 hours.

Adverse Events

Treatment-related adverse events occurred in 22.2% of the fosnetupitant group vs 25.4% of the fosaprepitant group, and were grade ≥ 3 in 2.6% vs 3.1%. Treatment-related adverse events occurring in ≥ 5% of patients in either the fosnetupitant or fosaprepitant groups were constipation (11.2% vs 13.7%) and hiccups (4.8% vs 7.1%). Overall, injection site reactions occurred in 11.0% vs 20.6% of patients (P < .001) and were considered treatment-related in 0.3% vs 3.6% (P < .001). No serious treatment-related adverse events were observed in the fosnetupitant group, with two—ischemic colitis and erythema multiforme—being observed in the fosaprepitant group.

The investigators concluded, “[Fosnetupitant] demonstrated noninferiority to [fosaprepitant], with a favorable safety profile and lower risk for injection site reactions. Thus, [fosnetupitant] is valuable in the prophylaxis of acute, delayed, and beyond delayed chemotherapy-induced nausea and vomiting.”

Akito Hata, MD, of the Department of Thoracic Oncology, Kobe Minimally Invasive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by Taiho Pharmaceutical Co, Ltd. For full disclosures of the study authors, visit ascopubs.org.