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 · 发表于：Signal Transduction and Targeted Therapy · 年份：2024 · DOI：10.1038/s41392-024-01948-4 · 被引用次数：31 · 研究领域：Pancreatic and Hepatic Oncology Research、Neuroendocrine Tumor Research Advances、Cholangiocarcinoma and Gallbladder Cancer Studies

Abstract 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...