盐酸伊立替康脂质体 HR070803 联合 5-氟尿嘧啶和白血病素治疗既往接受过吉西他滨治疗的局部晚期或转移性胰腺导管腺癌(PAN-HEROIC-1):3 期试验

IF 40.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
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
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引用次数: 0

摘要

脂质体伊立替康在既往接受过吉西他滨疗法的晚期或转移性胰腺导管腺癌(PDAC)患者中显示出良好的抗肿瘤活性。这项随机、双盲、平行对照、多中心3期研究(NCT05074589)评估了脂质体伊立替康HR070803联合5-氟尿嘧啶(5-FU)和亮菌素(LV)在该患者群体中的疗效和安全性。既往接受过吉西他滨疗法的不可切除、局部晚期或转移性PDAC患者按1:1比例随机接受HR070803(60毫克/平方米无水盐酸伊立替康,相当于56.5毫克/平方米游离碱)或安慰剂,两者均与5-FU(2000毫克/平方米)和LV(200毫克/平方米)联合使用,每两周静脉给药一次。研究的主要终点是总生存期(OS)。共有298名患者接受了HR070803加5-FU/LV(HR070803组,n=149)或安慰剂加5-FU/LV(安慰剂组,n=149)治疗。与安慰剂组相比,HR070803组的中位OS明显改善(7.4个月[95% CI 6.1-8.4]对5.0个月[95% CI 4.3-6.0];HR 0.63 [95% CI 0.48-0.84];双侧P = 0.0019)。HR070803组最常见的≥3级不良事件是γ-谷氨酰转移酶升高(19.0%,安慰剂组为11.6%)和中性粒细胞计数减少(12.9%,安慰剂组为0)。HR070803组未发生治疗相关死亡病例,而安慰剂组有一例治疗相关死亡病例(腹部感染)。HR070803联合5-FU/LV在二线治疗晚期或转移性PDAC方面显示出良好的疗效和可控的安全性,是该患者群体的一个潜在选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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/m2 anhydrous irinotecan hydrochloride, equal to 56.5 mg/m2 free base) or placebo, both in combination with 5-FU (2000 mg/m2) and LV (200 mg/m2), 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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来源期刊
Signal Transduction and Targeted Therapy
Signal Transduction and Targeted Therapy Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
44.50
自引率
1.50%
发文量
384
审稿时长
5 weeks
期刊介绍: Signal Transduction and Targeted Therapy is an open access journal that focuses on timely publication of cutting-edge discoveries and advancements in basic science and clinical research related to signal transduction and targeted therapy. Scope: The journal covers research on major human diseases, including, but not limited to: Cancer,Cardiovascular diseases,Autoimmune diseases,Nervous system diseases.
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