Randomized, Phase III Trial of Mixed Formulation of Fosrolapitant and Palonosetron (HR20013) in Preventing Cisplatin-Based Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: PROFIT.
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
{"title":"Randomized, Phase III Trial of Mixed Formulation of Fosrolapitant and Palonosetron (HR20013) in Preventing Cisplatin-Based Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: PROFIT.","authors":"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","doi":"10.1200/JCO-24-01308","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 <i>P</i> < .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% <i>v</i> 86.5%; two-sided <i>P</i> = .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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1123-1136"},"PeriodicalIF":42.1000,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/JCO-24-01308","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/2 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
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.
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.