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

• Published in: Journal of clinical oncology Vol. 40; no. 2; pp. 180 - 188
• Main Authors: Hata, Akito, Okamoto, Isamu, Inui, Naoki, Okada, Morihito, Morise, Masahiro, Akiyoshi, Kohei, Takeda, Masayuki, Watanabe, Yasutaka, Sugawara, Shunichi, Shinagawa, Naofumi, Kubota, Kaoru, Saeki, Toshiaki, Tamura, Tomohide
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health 10.01.2022
• Subjects: Adult; Aged; Aged, 80 and over; Antiemetics - adverse effects; Antiemetics - therapeutic use; Antineoplastic Agents - adverse effects; Cisplatin - adverse effects; Dexamethasone - therapeutic use; Double-Blind Method; Drug Combinations; Female; Humans; Isoquinolines - adverse effects; Isoquinolines - therapeutic use; Japan; Male; Middle Aged; Morpholines - adverse effects; Morpholines - therapeutic use; Nausea - chemically induced; Nausea - diagnosis; Nausea - prevention & control; Neurokinin-1 Receptor Antagonists - adverse effects; Neurokinin-1 Receptor Antagonists - therapeutic use; ORIGINAL REPORTS; Pyridines - adverse effects; Pyridines - therapeutic use; Quinuclidines - adverse effects; Quinuclidines - therapeutic use; Time Factors; Treatment Outcome; Vomiting - chemically induced; Vomiting - diagnosis; Vomiting - prevention & control; Japan
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/jco.21.01315

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 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). Overall, 795 patients were randomly assigned, of whom 785 received the study drug (FosNTP [N = 392] 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% ( < .001) and 0.3% versus 3.6% ( < .001), respectively. 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.