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

Zhengqing Lei; Weihu Ma; Anfeng Si; Yuhua Zhang; Facai Yang; Qiushi Yu; Haolan Tang; Qianru Xiao; Jiahua Zhou; Kui Wang; Yufu Tang; Tao Han; Guowen Yin; Jinhong Chen; Xiufeng Liu; Hua Zhao; Decai Yu; Tao Luo; Qing Wang; Maolin Yan; Xianhai Mao; Jing Li; Kai Wang; Jingdong Li; Yongyi Zeng; Dequan Ding; Tingsong Chen; Xiaofeng Wu; Yongxiang Xia; Kang Wang; Weixing Guo; Guangyu Zhu; Shan Gao; Norbert Hüser; Wan Y Lau; Tianqiang Song; Shuqun Cheng; Feng Shen; Zhangjun Cheng

doi:10.1111/apt.17623

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

Aliment Pharmacol Ther. 2023 Sep;58(6):611-622. doi: 10.1111/apt.17623. Epub 2023 Jun 22.

Authors

Zhengqing Lei¹, Weihu Ma¹, Anfeng Si², Yuhua Zhang³, Facai Yang¹, Qiushi Yu¹, Haolan Tang¹, Qianru Xiao¹, Jiahua Zhou¹, Kui Wang⁴, Yufu Tang⁵, Tao Han⁶, Guowen Yin⁷, Jinhong Chen⁸, Xiufeng Liu⁹, Hua Zhao¹⁰, Decai Yu¹¹, Tao Luo¹², Qing Wang¹³, Maolin Yan¹⁴, Xianhai Mao¹⁵, Jing Li¹⁶, Kai Wang¹⁷, Jingdong Li¹⁸, Yongyi Zeng¹⁹, Dequan Ding²⁰, Tingsong Chen²¹, Xiaofeng Wu²², Yongxiang Xia²², Kang Wang²³, Weixing Guo²³, Guangyu Zhu²⁴, Shan Gao²⁵, Norbert Hüser²⁶, Wan Y Lau²⁷, Tianqiang Song²⁸, Shuqun Cheng²³, Feng Shen²⁹, Zhangjun Cheng¹

Affiliations

¹ Hepato-Pancreato-Biliary Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
² Department of Surgical Oncology, Qin Huai Medical District of Jinling Hospital, Nanjing University, Nanjing, China.
³ Department of Hepatobiliary and Pancreatic Surgery, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou, China.
⁴ Department of Hepatic Surgery II, The Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
⁵ Department of Hepatobiliary Surgery, General Hospital of Northern Theater Command, Shenyang, China.
⁶ Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.
⁷ Interventional Radiology Department, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
⁸ Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China.
⁹ Department of Medical Oncology of PLA Cancer Center, Jinling Hospital, Nanjing, China.
¹⁰ Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
¹¹ Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
¹² Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Institute of Pathology and Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
¹³ Department of General Surgery, Zibo Central Hospital, Zibo, China.
¹⁴ Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China.
¹⁵ Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.
¹⁶ Department of Hepatobiliary, The Second Affiliated Hospital of Army Medical University, Chongqing, China.
¹⁷ Department of General Surgery, Jiangxi Provincial Clinical Research Center for General Surgery Disease, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
¹⁸ Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
¹⁹ Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fuzhou, China.
²⁰ Department of Interventional Radiology, Maanshan People's Hospital, Maanshan, China.
²¹ Department of Oncology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China.
²² Hepatobiliary Center, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
²³ Department of Hepatic Surgery VI, The Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
²⁴ Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
²⁵ Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University, Nanjing, China.
²⁶ Department of Surgery, TUM School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
²⁷ Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Special Administrative Region, China.
²⁸ Liver Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
²⁹ Department of Hepatic Surgery IV, The Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.

PMID: 37349908
DOI: 10.1111/apt.17623

Abstract

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.

Keywords: chemotherapy; combination therapy; immune checkpoint inhibitor; immunotherapy; intrahepatic cholangiocarcinoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bile Duct Neoplasms* / drug therapy
Bile Ducts, Intrahepatic
Cholangiocarcinoma* / drug therapy
Combined Modality Therapy
Humans
Immune Checkpoint Inhibitors / therapeutic use

Substances

Immune Checkpoint Inhibitors