Department of Thoracic Oncology, Kobe Minimally Invasive Cancer Center, Kobe, Japan.
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
J Clin Oncol. 2022 Jan 10;40(2):180-188. doi: 10.1200/JCO.21.01315. Epub 2021 Nov 18.
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.
我们评估了fosnetupitant（FosNTP）与fosaprepitant（FosAPR）预防高致吐性化疗引起的恶心和呕吐的疗效和安全性。这项 III 期研究是两种不同的神经激肽-1 受体拮抗剂与 palonosetron 和地塞米松联合应用的首次头对头比较。
计划接受顺铂为基础的化疗的患者按 1:1 随机分配接受 FosNTP 235mg 或 FosAPR 150mg 联合 palonosetron 0.75mg 和地塞米松。主要终点是总体（0-120 小时）完全缓解（CR；无恶心事件和无解救药物）率，按性别和年龄类别分层，以显示 FosNTP 不劣于 FosAPR（非劣效性边界，总体 CR 率差异-10%）。
共有 795 例患者被随机分配，其中 785 例接受了研究药物（FosNTP[N=392]FosAPR[N=393]），并进行了疗效和安全性评估。总体 CR 率分别为 75.2%和 71.0%（Mantel-Haenszel 共同风险差，4.1%；95%CI，-2.1%至 10.3%），表明 FosNTP 不劣于 FosAPR。急性（0-24 小时）、延迟（24-120 小时）和延迟后（120-168 小时）以及 0-168 小时的 CR 率分别为 93.9%和 92.6%、76.8%和 72.8%、86.5%和 81.4%和 73.2%和 66.9%。FosNTP 与 FosAPR 相比，治疗相关不良事件的发生率分别为 22.2%和 25.4%，而与注射部位反应相关的不良事件或治疗相关不良事件分别为 11.0%和 20.6%（<0.001）和 0.3%和 3.6%（<0.001）。
FosNTP 与 FosAPR 相比具有非劣效性，安全性良好，注射部位反应风险较低。因此，FosNTP 在预防急性、延迟和延迟后化疗引起的恶心和呕吐方面具有重要价值。
