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

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<sup>2</sup> anhydrous irinotecan hydrochloride, equal to 56.5 mg/m<sup>2</sup> free base) or placebo, both in combination with 5-FU (2000 mg/m<sup>2</sup>) and LV (200 mg/m<sup>2</sup>), 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.

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Publication Details

Journal
Signal Transduction and Targeted Therapy
Published
2024-09-19
DOI
https://doi.org/10.1038/s41392-024-01948-4
Citations
20
Primary Topic
Pancreatic and Hepatic Oncology Research
Type
article
Field-Weighted Citation Impact
5.65
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article

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

Deliang Fu, Chuntao Gao, Jun Zhou, Weijia Fang et al.
20 citations
Signal Transduction and Targeted Therapy
Pancreatic and Hepatic Oncology Research
5.65
article

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

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

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<sup>2</sup> anhydrous irinotecan hydrochloride, equal to 56.5 mg/m<sup>2</sup> free base) or placebo, both in combination with 5-FU (2000 mg/m<sup>2</sup>) and LV (200 mg/m<sup>2</sup>), 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.

Signal Transduction and Targeted TherapyVol. 9(1)
Qingdao University (CN), Union Hospital (HK), Shanghai Medical College of Fudan University (CN), Harbin Medical University (CN), Sun Yat-sen University (CN), Jilin University (CN), Anhui Medical University (CN), Peking University (CN), Sichuan University (CN), Fudan University (CN), Renji Hospital (CN), Tianjin Medical University General Hospital (CN), Tianjin Medical University Cancer Institute and Hospital (CN), First Affiliated Hospital of Xiamen University (CN), West China Hospital of Sichuan University (CN), Peking University Cancer Hospital (CN), Sun Yat-sen Memorial Hospital (CN), Shandong Tumor Hospital (CN), Third Affiliated Hospital of Harbin Medical University (CN), Shanghai Cancer Institute (CN), Affiliated Hospital of Qingdao University (CN), First Affiliated Hospital of Xi'an Jiaotong University (CN), First Hospital of Jilin University (CN), Zhongshan Hospital (CN), Jiangsu Cancer Hospital (CN), Anhui Provincial Hospital (CN), Zhejiang Provincial People's Hospital (CN), Yanbian University Hospital (CN), First Affiliated Hospital of Henan University of Science and Technology (CN), First Affiliated Hospital of Anhui Medical University (CN), Henan Cancer Hospital (CN), Affiliated Zhongshan Hospital of Dalian University (CN), Jiangsu Hengrui Medicine (China) (CN), Affiliated Hangzhou First People's Hospital, Westlake University, School of Medicine (CN), Second Affiliated Hospital of Anhui Medical University (CN), Huashan Hospital (CN), Shandong First Medical University (CN), First Affiliated Hospital Zhejiang University (CN), Huazhong University of Science and Technology (CN)
Good health and well-being
Openalex Percentile: Top 3%
Pancreatic and Hepatic Oncology Research
5.65
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