Randomized, Phase III Trial of Mixed Formulation of Fosrolapitant and Palonosetron (HR20013) in Preventing Cisplatin-Based Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: PROFIT
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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (38)
Huaqiang Zhou
Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
Yuanyuan Zhao
College of Chemistry
Mingjun Zhang
Jun Yao
Key Lab of Mesoscopic Chemistry, School of Chemistry and Chemical Engineering
Shuang Leng
Xiumin Li
Linyi Cancer Hospital Linyi China
Li Lin
Jinping Chen
Songnan Zhang
Xia Qin
1Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Blood and Marrow Transplantation Center, Shanghai, China
Zhiquan Qin
Department of Oncology, Zhejiang Provincial People’s Hospital, Hangzhou, China
Tienan Yi
Ruoyu Wang
Xiang Li
Yan Yu
Department of Respiratory Oncology Harbin Medical University Cancer Hospital Harbin China
Zhenghua Wang
The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China
Qinhong Zheng
Jiazhuan Mei
Department of Oncology, Zhengzhou People's Hospital, Zhengzhou, China
Aimin Zang
Department of Oncology, Affiliated Hospital of Hebei University, Baoding, China
Na Li
Fengjun Cao
Department of Oncology, Shiyan People's Hospital, Shiyan, China
Ke Cao
Institute of Analytical Chemistry and Instrument for Life Science, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology
Weiwei Li
Beijing University of Chemical Technology , , ,
Yanda Lu
Department of Oncology, The First Affiliated Hospital of Hainan Medical University, Haikou, China
Dang Lin
Respiratory Medicine Department, Suzhou Municipal Hospital, Suzhou, China
Yan Zhou
Runxiang Yang
Department of Internal Medicine I, Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, China
Wenfeng Fang
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China
Ningning Zhou
State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering
Yunpeng Yang
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China
Yaxiong Zhang
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
Gang Chen
Ting Zhou
Xue Yang
Huan Wang
Yujiao Wang
Yan Huang
Li Zhang