Irinotecan hydrochloride liposome HR070803 in combination with 5-fluorouracil and leucovorin in locally advanced or metastatic pancreatic ductal adenocarcinoma following prior gemcitabine-based therapy (PAN-HEROIC-1): a phase 3 trial  

作　　者：Jiujie Cui Shukui Qin Yuhong Zhou Shuang Zhang Xiaofeng Sun Mingjun Zhang Jiuwei Cui Weijia Fang Kangsheng Gu Zhihua Li Jufeng Wang Xiaobing Chen Jun Yao Jun Zhou Gang Wang Yuxian Bai Juxiang Xiao Wensheng Qiu Bangmao Wang Tao Xia Chunyue Wang Li Kong Jiajun Yin Tao Zhang Xionghu Shen Deliang Fu Chuntao Gao Huan Wang Quanren Wang Liwei Wang 

机构地区：[1]Oncology Department and State Key Laboratory of Systems Medicine for Cancer of Shanghai Cancer Institute,Renji Hospital,School of Medicine,Shanghai Jiaotong University,Shanghai,China [2]GI Cancer Center,Nanjing Tianyinshan Hospital,China Pharmaceutical University,Nanjing,China [3]Medical Oncology,Zhongshan Hospital Affiliated with Fudan University,Shanghai,China [4]Department of Biotherapy,West China School of Medicine/West China Hospital of Sichuan University,Chengdu,China [5]Internal Medicine,Jiangsu Cancer Hospital&Jiangsu Institute of Cancer Research&The Affiliated Cancer Hospital of Nanjing Medical University,Nanjing,China [6]Medical Oncology,The Second Affiliated Hospital of Anhui Medical University,Hefei,China [7]Department of Oncology,The First Hospital of Jilin University,Changchun,China [8]Medical Oncology III,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China [9]Medical Oncology,The First Affiliated Hospital of Anhui Medical University,Hefei,China [10]Department of Oncology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou,China [11]Department of Oncology,The Affiliated Cancer Hospital,Zhengzhou University,Zhengzhou,China [12]Department of Oncology,The First Affiliated Hospital of Henan University of Science and Technology,Luoyang,China [13]Department of Gastrointestinal Oncology,Peking University Cancer Hospital&Institute,Beijing,China [14]Department of Oncology,The First Affiliated Hospital of USTC Anhui Provincial Hospital,Hefei,China [15]Department of Oncology,Harbin Medical University Cancer Hospital,Harbin,China [16]Medical Oncology,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an,China [17]Department of Oncology,The Affiliated Hospital of Qingdao University,Qingdao,China [18]Department of Gastroenterology,Tianjin Medical University General Hospital,Tianjin,China [19]Division of Gastrointestinal and Pancreatic Surgery,Zhejiang Provincial People’s Hospital,Hangzhou,China [20]Medical Oncology,The First Affiliated Hospital of Xia

出　　处：《Signal Transduction and Targeted Therapy》2024年第10期4628-4636,共9页信号转导与靶向治疗（英文）

基　　金：Jiangsu Hengrui Pharmaceuticals Co.,Ltd.

摘　　要：Liposomal irinotecan has shown promising antitumor activity in patients with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) who have undergone prior gemcitabine-based therapies. This randomized, double-blind, parallel-controlled, multicenter phase 3 study (NCT05074589) assessed the efficacy and safety of liposomal irinotecan HR070803 combined with 5-fluorouracil (5-FU) and leucovorin (LV) in this patient population. Patients with unresectable, locally advanced, or metastatic PDAC who had previously received gemcitabine-based therapies were randomized 1:1 to receive either HR070803 (60 mg/m^(2) anhydrous irinotecan hydrochloride, equal to 56.5 mg/m^(2) free base) or placebo, both in combination with 5-FU (2000 mg/m^(2)) and LV (200 mg/m^(2)), all given intravenously every two weeks. The primary endpoint of the study was overall survival (OS). A total of 298 patients were enrolled and received HR070803 plus 5-FU/LV (HR070803 group, n = 149) or placebo plus 5-FU/LV (placebo group, n = 149). Median OS was significantly improved in the HR070803 group compared to the placebo group (7.4 months [95% CI 6.1–8.4] versus 5.0 months [95% CI 4.3–6.0];HR 0.63 [95% CI 0.48–0.84];two-sided p = 0.0019). The most common grade ≥ 3 adverse events in the HR070803 group were increased gamma-glutamyltransferase (19.0% versus 11.6% in placebo group) and decreased neutrophil count (12.9% versus 0 in placebo group). No treatment-related deaths occurred in the HR070803 group, while the placebo group reported one treatment-related death (abdominal infection). HR070803 in combination with 5-FU/LV has shown promising efficacy and manageable safety in advanced or metastatic PDAC in the second-line setting, representing a potential option in this patient population.

关 键 词：METASTATIC adenocarcinoma sided 

分 类 号：R735.9[医药卫生—肿瘤]