Retrospective Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2023; 15(4): 689-699
Published online Apr 15, 2023. doi: 10.4251/wjgo.v15.i4.689
Correlation between immune-related adverse events and long-term outcomes in pembrolizumab-treated patients with unresectable hepatocellular carcinoma: A retrospective study
Jiang-Min Zhou, Hui-Fang Xiong, Xiao-Ping Chen, Zhi-Wei Zhang, Li-Ping Zhu, Biao Wu
Jiang-Min Zhou, Li-Ping Zhu, Biao Wu, Department of Hepatobiliary Surgery, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan 430030, Hubei Province, China
Hui-Fang Xiong, Department of Digestive Medicine, Dongxihu District People’s Hospital, Wuhan 430030, Hubei Province, China
Xiao-Ping Chen, Zhi-Wei Zhang, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Author contributions: Zhou JM and Xiong HF analyzed the data and wrote the manuscript; Zhu LP, Zhang ZW, and Chen XP designed the research; Wu B modified the manuscript; and all authors read and approved the final manuscript.
Institutional review board statement: The study was approved by the Ethical Committee of Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology. All procedures performed in this study abided by the Declaration of Helsinki.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets (data) for this study can be found in the (figure) https://figshare.com/s/ee63fa5271448d51104e. The other datasets were available on request from the corresponding author at wuhanyywb@163.com.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Biao Wu, MD, Doctor, Department of Hepatobiliary Surgery, Wuhan Hospital of Traditional Chinese and Western Medicine, No. 215 Zhongshan Avenue, Qiaokou District, Wuhan 430030, Hubei Province, China. wuhanyywb@163.com
Received: October 26, 2022
Peer-review started: October 26, 2022
First decision: December 14, 2022
Revised: December 16, 2022
Accepted: March 23, 2023
Article in press: March 23, 2023
Published online: April 15, 2023
Processing time: 167 Days and 23.7 Hours
Abstract
BACKGROUND

Although immune checkpoint inhibitor (ICI) therapy has improved the prognosis of unresectable hepatocellular carcinoma (HCC), it has also resulted in unique immune-related adverse events (irAEs). The relationship between irAE and treatment outcomes in ICI-treated unresectable HCC patients remains unknown.

AIM

To elucidate the correlation between immune-related toxic effects and prognosis in patients with unresectable HCC treated with pembrolizumab.

METHODS

From March 2019 to February 2021, a total of 190 unresectable HCC (Barcelona Clinic Liver Cancer C) patients receiving pembrolizumab treatment were retrospectively reviewed. Overall survival (OS) was the primary endpoint, while objective response rate (ORR), disease control rate (DCR), and time to progression (TTP) were secondary evaluation indexes. We assessed demographics, irAEs, and outcomes by retrospective review.

RESULTS

One hundred and forty-three males and 47 females were included in the study. The ORR and DCR were 12.1% (23/190) and 52.1% (99/190), respectively. The median OS was 376 d [95% confidence interval (CI): 340-411 d] and the median TTP was 98 d (95%CI: 75-124 d). The overall incidence of treatment-related adverse events was 72.6% (138/190) and 10.0% of them were severe irAEs (grade ≥ 3). Child-Pugh B class, portal vein tumor thrombus, extrahepatic metastasis, and hypothyroidism were the independent risk factors for survival. Patients with hypothyroidism showed a longer OS [517 d (95%CI: 423-562) vs 431 d (95%CI: 412-485), P = 0.011] and TTP [125 d (95%CI: 89-154) vs 87 d (95%CI: 61-98), P = 0.004] than those without irAEs.

CONCLUSION

Pembrolizumab-treated patients with unresectable HCC who experienced hypothyroidism have promising ORR and durable response. Hypothyroidism, an irAE, may be used as a clinical evaluation parameter of response to ICIs in unresectable HCC.

Keywords: Hepatocellular carcinoma; Immune checkpoint inhibitors; Pembrolizumab; Immune-related adverse events; Overall survival; Retrospective study

Core Tip: This is a retrospective study to elucidate the correlation between immune-related toxic effects and prognosis in patients with unresectable hepatocellular carcinoma (HCC) treated with pembrolizumab. One hundred and forty-three male patients and forty-seven female patients were included in the study. The overall incidence of treatment-related adverse events was 72.6% (138/190) and 10.0% of them were severe immune-related adverse events (irAEs) (grade ≥ 3). Patients with hypothyroidism were observed to have a longer overall survival and time to progression than those without irAEs. Unresectable HCC patients who experienced hypothyroidism had a better therapeutic effect.