Effect of different PD-1 inhibitor combination therapies for unresectable intrahepatic cholangiocarcinoma

被引：9

作者：

Lei, Zhengqing ^{[1
]}

Ma, Weihu ^{[1
]}

Si, Anfeng ^{[2
]}

Zhang, Yuhua ^{[3
]}

Yang, Facai ^{[1
]}

Yu, Qiushi ^{[1
]}

Tang, Haolan ^{[1
]}

Xiao, Qianru ^{[1
]}

Zhou, Jiahua ^{[1
]}

Wang, Kui ^{[4
]}

Tang, Yufu ^{[5
]}

Han, Tao ^{[6
]}

Yin, Guowen ^{[7
]}

Chen, Jinhong ^{[8
,9
]}

Liu, Xiufeng ^{[10
]}

Zhao, Hua ^{[11
]}

Yu, Decai ^{[12
]}

Luo, Tao ^{[13
,14
]}

Wang, Qing ^{[15
]}

Yan, Maolin ^{[16
]}

Mao, Xianhai ^{[17
]}

Li, Jing ^{[18
]}

Wang, Kai ^{[19
]}

Li, Jingdong ^{[20
]}

Zeng, Yongyi ^{[21
]}

Ding, Dequan ^{[22
]}

Chen, Tingsong ^{[23
]}

Wu, Xiaofeng ^{[24
]}

Xia, Yongxiang ^{[24
]}

Wang, Kang ^{[25
]}

Guo, Weixing ^{[25
]}

Zhu, Guangyu ^{[26
]}

Gao, Shan ^{[27
]}

Hueser, Norbert ^{[28
]}

Lau, Wan Y. ^{[29
]}

Song, Tianqiang ^{[30
]}

Cheng, Shuqun ^{[25
]}

Shen, Feng ^{[31
]}

Cheng, Zhangjun ^{[1
]}

机构：

[1] Southeast Univ, Zhongda Hosp, Hepatopancreatobiliary Ctr, Sch Med, Nanjing 210009, Peoples R China

[2] Nanjing Med Univ, Dept Surg Oncol, Qin Huai Med Dist, Jinling Hosp, Nanjing, Peoples R China

[3] Chinese Acad Sci, Univ Chinese Acad Sci, Zhejiang Canc Hosp, Dept Hepatobiliary & Pancreat Surg,Inst Basic Med, Hangzhou, Peoples R China

[4] Naval Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Hepat Surg 2, Shanghai, Peoples R China

[5] Northern Theater Command, Dept Hepatobiliary Surg, Gen Hosp, Shenyang, Peoples R China

[6] China Med Univ, Dept Med Oncol, Hosp 1, Shenyang, Peoples R China

[7] Nanjing Med Univ, Jiangsu Canc Hosp, Jiangsu Inst Canc Res, Intervent Radiol Dept,Affiliated Canc Hosp, Nanjing, Peoples R China

[8] Fudan Univ, Huashan Hosp, Dept Gen Surg, Shanghai, Peoples R China

[9] Fudan Univ, Canc Metastasis Inst, Shanghai, Peoples R China

[10] Jinling Hosp, Dept Med Oncol, PLA Canc Ctr, Nanjing, Peoples R China

[11] Soochow Univ, Dept Gen Surg, Affiliated Hosp 1, Suzhou, Peoples R China

[12] Nanjing Univ, Affiliated Drum Tower Hosp, Dept Hepatobiliary Surg, Med Sch, Nanjing, Peoples R China

[13] Third Mil Med Univ, Army Med Univ, Inst Pathol, Minist Educ China,Key Lab Tumor Immunopathol, Chongqing, Peoples R China

[14] Third Mil Med Univ, Army Med Univ, Southwest Hosp, Chongqing, Peoples R China

[15] Zibo Cent Hosp, Dept Gen Surg, Zibo, Peoples R China

[16] Fujian Prov Hosp, Dept Hepatobiliary Pancreat Surg, Fuzhou, Peoples R China

[17] Hunan Normal Univ, Hunan Prov Peoples Hosp, Dept Hepatobiliary Surg, Affiliated Hosp 1, Changsha, Peoples R China

[18] Army Med Univ, Dept Hepatobiliary, Affiliated Hosp 2, Chongqing, Peoples R China

[19] Nanchang Univ, Jiangxi Prov Clin Res Ctr Gen Surg Dis, Dept Gen Surg, Affiliated Hosp 2, Nanchang, Peoples R China

[20] North Sichuan Med Coll, Dept Hepatobiliary Surg, Affiliated Hosp, Nanchong, Peoples R China

[21] Fujian Med Univ, Mengchao Hepatobiliary Hosp, Dept Hepatobiliary Surg, Fuzhou, Peoples R China

[22] Maanshan Peoples Hosp, Dept Intervent Radiol, Maanshan, Peoples R China

[23] Shanghai Univ Tradit Chinese Med, Dept Oncol, Peoples Hosp 7, Shanghai, Peoples R China

[24] Nanjing Med Univ, Chinese Acad Med Sci, Hepatobiliary Ctr, Affiliated Hosp 1,Key Lab Liver Transplantat,NHC K, Nanjing, Peoples R China

[25] Naval Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Hepat Surg 6, Shanghai, Peoples R China

[26] Southeast Univ, Zhongda Hosp, Ctr Intervent Radiol & Vasc Surg, Sch Med,Dept Radiol, Nanjing, Peoples R China

[27] Southeast Univ, Zhongda Hosp, Adv Inst Life & Hlth, Sch Life Sci & Technol, Nanjing, Peoples R China

[28] Tech Univ Munich, TUM Sch Med, Dept Surg, Klinikum Rechts Isar, Munich, Germany

[29] Chinese Univ Hong Kong, Fac Med, Hong Kong, Peoples R China

[30] Tianjin Med Univ Canc Inst & Hosp, Liver Canc Ctr, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy,Tianjins Clin Res, Tianjin 300060, Peoples R China

[31] Naval Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Hepat Surg 4, Shanghai 200438, Peoples R China

来源：

ALIMENTARY PHARMACOLOGY & THERAPEUTICS | 2023年 / 58卷 / 06期

基金：

中国国家自然科学基金;

关键词：

chemotherapy; combination therapy; immune checkpoint inhibitor; immunotherapy; intrahepatic cholangiocarcinoma; HEPATOCELLULAR-CARCINOMA; OPEN-LABEL; PLUS; BEVACIZUMAB;

D O I：

10.1111/apt.17623

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background: Immune checkpoint inhibitor (ICI) combination therapy offers a new option for treatment of unresectable intrahepatic cholangiocarcinoma (uICC).Aim: To compare the effect of different anti-PD-1 combination therapies as the first-line treatments for uICC.Methods: This study included 318 patients who received chemotherapy alone (Chemo), anti-PD-1 plus chemotherapy (ICI-chemo), anti-PD-1 plus targeted therapy (ICI-target) or anti-PD-1 plus targeted therapy and chemotherapy (ICI-target-chemo) as first line for uICC from 22 centres in China. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR) and safety.Results: Patients with ICI-chemo (median PFS [mPFS], 6.3 months; HR: 0.61, 95% CI: 0.42-0.88; p = 0.008; median OS [mOS], 10.7 months; HR: 0.61, 95% CI: 0.39-0.94; p = 0.026), ICI-target (7.2 months; HR: 0.54, 95% CI: 0.36-0.80; p = 0.002; 15.8 months; HR: 0.54, 95% CI: 0.35-0.84; p = 0.006) or ICI-target-chemo (6.9 months; HR: 0.65, 95% CI: 0.47-0.90; p = 0.009; 14.4 months; HR: 0.47, 95% CI: 0.31-0.70; p < 0.001) achieved better clinical outcomes than those with Chemo (3.8 months; 9.3 months). ICI-target was not inferior to ICI-chemo in survival outcomes (HR for PFS: 0.88, 95% CI: 0.55-1.42; p = 0.614; HR for OS: 0.89, 95% CI: 0.51-1.55; p = 0.680). ICI-target-chemo yielded similar prognoses as ICI-chemo (HR for PFS: 1.07, 95% CI: 0.70-1.62; p = 0.764; HR for OS: 0.77, 95% CI: 0.45-1.31; p = 0.328) and ICI-target (HR for PFS: 1.20, 95% CI: 0.77-1.88; p = 0.413; HR for OS: 0.86, 95% CI: 0.51-1.47; p = 0.583) but resulted in more adverse events (p < 0.001; p = 0.010). Multivariable and propensity score analyses supported these findings.Conclusions: Among patients with uICC, ICI-chemo or ICI-target provided more survival benefits than Chemo while achieving comparable prognoses and fewer adverse events than ICI-target-chemo.

引用

页码：611 / 622

页数：12

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