Randomized, Phase III Trial of Mixed Formulation of Fosrolapitant and Palonosetron (HR20013) in Preventing Cisplatin-Based Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: PROFIT

作者：Huaqiang Zhou, Yuanyuan Zhao, Mingjun Zhang, Jun Yao, Shuang Leng, Xiu-Min Li, Lin Li, J Chen, Songnan Zhang, Xia Qin, Zhiquan Qin, Tienan Yi, Ruoyu Wang, Xiang Li, Yan Yu, Zhenghua Wang, Qinhong Zheng, Jiazhuan Mei, Aimin Zang, Na Li, Fengjun Cao, Ke Cao, Weiwei Li, Yanda Lu, Dang Lin, Yan Zhou, Runxiang Yang, Wenfeng Fang, Ningning Zhou, Yunpeng Yang, Yaxiong Zhang, Gang Chen, Ting Zhou, Xue Yang, Huan Wang, Yujiao Wang, Yan Huang, Li Zhang · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco-24-01308 · 被引用次数：9 · 研究领域：Nausea and vomiting management、Chemotherapy-induced organ toxicity mitigation、Enhanced Recovery After Surgery

PURPOSE Mixed formulation of fosrolapitant and palonosetron (PALO), HR20013, is a novel fixed-dose intravenous antiemetic combination that could simultaneously antagonize neurokinin-1 and 5-hydroxytryptamine-3 receptors. This study was designed to evaluate the efficacy and safety of HR20013 plus dexamethasone (DEX) versus fosaprepitant (FAPR) plus PALO + DEX for preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC). METHODS This is a noninferiority study. Chemotherapy-naïve patients were randomly assigned 1:1 to receive HR20013 (day 1) or FAPR + PALO (day 1) before each cycle of cisplatin-based HEC (two cycles in total), together with oral DEX (day 1-4). The primary end point was overall (0-120 hours) complete response (CR; no vomiting/no rescue therapy) rate in cycle 1. The key secondary end point was CR rate at the beyond delayed phase (120-168 hours) in cycle 1. RESULTS Three hundred seventy-three patients were enrolled to receive HR20013 + DEX and 377 to FAPR + PALO + DEX. The overall CR rate in cycle 1 was 77.7% for HR20013 + DEX and 78.2% for FAPR + PALO + DEX (difference = –0.9% [95% CI, –6.7 to 5.0]; one-sided P < .01), demonstrating that HR20013 + DEX was noninferior to FAPR + PALO + DEX. The superiority of HR20013 + DEX over FAPR + PALO + DEX in CR rate at the beyond delayed phase in cycle 1 was not met (90.3% v 86.5%; two-sided P = .11). In cycle 2, HR20013 + DEX showed greater proportions of patien...