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 

作者机构：Oncology Department and State Key Laboratory of Systems Medicine for Cancer of Shanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiaotong UniversityShanghaiChina GI Cancer CenterNanjing Tianyinshan HospitalChina Pharmaceutical UniversityNanjingChina Medical OncologyZhongshan Hospital Affiliated with Fudan UniversityShanghaiChina Department of BiotherapyWest China School of Medicine/West China Hospital of Sichuan UniversityChengduChina Internal MedicineJiangsu Cancer Hospital&Jiangsu Institute of Cancer Research&The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjingChina Medical OncologyThe Second Affiliated Hospital of Anhui Medical UniversityHefeiChina Department of OncologyThe First Hospital of Jilin UniversityChangchunChina Medical Oncology IIIThe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina Medical OncologyThe First Affiliated Hospital of Anhui Medical UniversityHefeiChina Department of OncologySun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouChina Department of OncologyThe Affiliated Cancer HospitalZhengzhou UniversityZhengzhouChina Department of OncologyThe First Affiliated Hospital of Henan University of Science and TechnologyLuoyangChina Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijingChina Department of OncologyThe First Affiliated Hospital of USTC Anhui Provincial HospitalHefeiChina Department of OncologyHarbin Medical University Cancer HospitalHarbinChina Medical OncologyThe First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina Department of OncologyThe Affiliated Hospital of Qingdao UniversityQingdaoChina Department of GastroenterologyTianjin Medical University General HospitalTianjinChina Division of Gastrointestinal and Pancreatic SurgeryZhejiang Provincial People’s HospitalHangzhouChina Medical OncologyThe First Affiliated Hospital of Xiamen UniversityXiamenChina Department of OncologyShandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanChina General SurgeryAffiliated Zhongshan Hospital of Dalian UniversityDalianChina Cancer CenterUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of OncologyAffiliated Hospital of Yanbian UniversityYanjiChina Pancreatic SurgeryHuashan HospitalFudan UniversityShanghaiChina Pancreatic SurgeryTianjin Medical University Cancer Institute&HospitalTianjinChina Jiangsu Hengrui Pharmaceuticals Co.LtdShanghaiChina 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2024年第9卷第10期

页      面：4628-4636页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Jiangsu Hengrui Pharmaceuticals Co. Ltd 

主　　题：metastatic adenocarcinoma sided 

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.