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

IF 42.1 1区医学 Q1 ONCOLOGY Journal of Clinical Oncology Pub Date : 2025-03-20 Epub Date: 2024-12-02 DOI:10.1200/JCO-24-01308

Huaqiang Zhou, Yuanyuan Zhao, Mingjun Zhang, Jun Yao, Shuang Leng, Xiumin Li, Li Lin, Jinping 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

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引用次数: 0

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 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 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.

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福洛匹坦和帕洛诺司酮（HR20013）混合配方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。

目的：氟吡坦与帕洛诺司琼（PALO）（HR20013）混合制剂是一种新型静脉固定剂量止吐剂，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fosaprepitant （FAPR）联合PALO + DEX在接受高度致吐性化疗（HEC）患者中预防化疗诱导的恶心和呕吐（CINV）的有效性和安全性。方法：这是一项非劣效性研究。Chemotherapy-naïve患者按1:1的比例随机分配，在每个顺铂类HEC周期（共两个周期）前接受HR20013（第1天）或FAPR + PALO（第1天），同时口服DEX（第1-4天）。主要终点为总（0-120小时）完全缓解(CR；第1周期无呕吐/无抢救治疗)率。关键的次要终点是第1周期延迟期（120-168小时）的CR率。结果：373例患者接受HR20013 + DEX治疗，377例患者接受FAPR + PALO + DEX治疗。第1周期的总CR率HR20013 + DEX为77.7%，FAPR + PALO + DEX为78.2%(差异= -0.9% [95% CI, -6.7至5.0]；单侧P < 0.01)，表明HR20013 + DEX不低于FAPR + PALO + DEX。HR20013 + DEX与FAPR + PALO + DEX相比，在第1周期延迟期后的CR率未达到优势(90.3% vs 86.5%；双侧P = .11)。在第2周期，与FAPR + PALO + DEX相比，HR20013 + DEX在延迟期（24-120小时）和延迟期之后报告对日常生活没有影响的患者比例更高。HR20013 + DEX组治疗相关不良事件发生率在第1周期为35.7%，在整个研究期间为42.1%，而FAPR + PALO + DEX组为38.2%和44.0%。结论：HR20013 + DEX对HEC-CINV的预防效果不低于FAPR + PALO + DEX，且耐受性良好，具有降低CINV对日常生活影响的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Oncology 医学-肿瘤学

CiteScore

41.20

自引率

2.20%

发文量

8215

审稿时长

2 months

期刊介绍： The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.