福沙吡坦与帕洛诺司琼混合制剂（HR20013）预防基于顺铂的高致吐性化疗引起的恶心和呕吐的随机III期试验：PROFIT

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

作者信息

Zhou Huaqiang, Zhao Yuanyuan, Zhang Mingjun, Yao Jun, Leng Shuang, Li Xiumin, Lin Li, Chen Jinping, Zhang Songnan, Qin Xia, Qin Zhiquan, Yi Tienan, Wang Ruoyu, Li Xiang, Yu Yan, Wang Zhenghua, Zheng Qinhong, Mei Jiazhuan, Zang Aimin, Li Na, Cao Fengjun, Cao Ke, Li Weiwei, Lu Yanda, Lin Dang, Zhou Yan, Yang Runxiang, Fang Wenfeng, Zhou Ningning, Yang Yunpeng, Zhang Yaxiong, Chen Gang, Zhou Ting, Yang Xue, Wang Huan, Wang Yujiao, Huang Yan, Zhang Li

机构信息

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Department of Oncology, The Second Hospital of Anhui Medical University, Hefei, China.

出版信息

J Clin Oncol. 2025 Mar 20;43(9):1123-1136. doi: 10.1200/JCO-24-01308. Epub 2024 Dec 2.

DOI:10.1200/JCO-24-01308

PMID:39621965

Abstract

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 < .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% 86.5%; two-sided = .11). In cycle 2, HR20013 + DEX showed greater proportions of patients reporting no impact on daily life at the delayed (24-120 hours) and beyond delayed phases compared with FAPR + PALO + DEX. The incidences of treatment-related adverse events were 35.7% during cycle 1 and 42.1% during entire study for HR20013 + DEX, versus 38.2% and 44.0% for FAPR + PALO + DEX.

CONCLUSION

HR20013 + DEX was noninferior to FAPR + PALO + DEX for preventing HEC-CINV and well tolerated, with the potential to reduce the impact of CINV on daily life.

摘要

目的

福沙吡坦和帕洛诺司琼（PALO）的混合制剂HR20013是一种新型的固定剂量静脉注射用止吐联合药物，可同时拮抗神经激肽-1和5-羟色胺-3受体。本研究旨在评估HR20013联合地塞米松（DEX）与福沙匹坦（FAPR）联合PALO + DEX预防接受高致吐性化疗（HEC）患者化疗引起的恶心和呕吐（CINV）的疗效和安全性。

方法

这是一项非劣效性研究。未接受过化疗的患者被随机1:1分配，在每周期基于顺铂的HEC（共两个周期）前第1天接受HR20013或FAPR + PALO，并口服DEX（第1 - 4天）。主要终点是第1周期的总体（0 - 120小时）完全缓解（CR；无呕吐/无补救治疗）率。关键次要终点是第1周期延迟后期（120 - 168小时）的CR率。

结果

373例患者接受HR20013 + DEX，377例接受FAPR + PALO + DEX。HR20013 + DEX组第1周期的总体CR率为77.7%，FAPR + PALO + DEX组为78.2%（差异 = -0.9% [95%CI，-6.7至5.0]；单侧P <.01），表明HR20013 + DEX不劣于FAPR + PALO + DEX。未达到HR20013 + DEX在第1周期延迟后期CR率优于FAPR + PALO + DEX的结果（90.3%对86.5%；双侧P =.11）。在第2周期，与FAPR + PALO + DEX相比，HR20013 + DEX组在延迟期（24 - 120小时）和延迟后期报告对日常生活无影响的患者比例更高。HR20013 + DEX组第1周期治疗相关不良事件发生率为35.7%，整个研究期间为42.1%，而FAPR + PALO + DEX组分别为38.2%和44.0%。