Transarterial Chemoembolization with Epirubicin-Loaded Microspheres for Hepatocellular Carcinoma: A Prospective, Single-Arm, Multicenter, Phase 2 Study (STOPPER Trial)

Hai-Dong Zhu; Xiao Li; Jun-Hui Sun; Xu Zhu; Zhao-Yu Liu; Hai-Liang Li; Jian Lu; Zhi-Ping Yan; Guo-Liang Shao; Xiao-Feng He; Min Chao; Li-Gong Lu; Bin-Yan Zhong; Rui Li; Qi Zhang; Gao-Jun Teng

doi:10.1007/s00270-024-03666-4

Transarterial Chemoembolization with Epirubicin-Loaded Microspheres for Hepatocellular Carcinoma: A Prospective, Single-Arm, Multicenter, Phase 2 Study (STOPPER Trial)

Cardiovasc Intervent Radiol. 2024 Mar;47(3):325-336. doi: 10.1007/s00270-024-03666-4. Epub 2024 Feb 27.

Authors

Hai-Dong Zhu^#¹, Xiao Li^#², Jun-Hui Sun^#³, Xu Zhu^#⁴, Zhao-Yu Liu^#⁵, Hai-Liang Li^#⁶, Jian Lu^#¹, Zhi-Ping Yan⁷, Guo-Liang Shao⁸, Xiao-Feng He⁹, Min Chao¹⁰, Li-Gong Lu¹¹, Bin-Yan Zhong¹², Rui Li¹, Qi Zhang¹, Gao-Jun Teng¹³

Affiliations

¹ Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
² Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
³ Division of Hepatobiliary and Pancreatic Surgery, Hepatobiliary and Pancreatic Interventional Treatment Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁴ Interventional Therapy Department, Peking University Cancer Hospital and Institute, Beijing, China.
⁵ Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China.
⁶ Department of Minimal-Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
⁷ Department of Interventional Radiology, Zhongshan Hospital, Fudan University Shanghai Institution of Medical Imaging, Fudan University, Shanghai, China.
⁸ Department of Intervention, The 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.
⁹ Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
¹⁰ Department of Radiology, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China.
¹¹ Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China.
¹² Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
¹³ Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China. gjteng@seu.edu.cn.

^# Contributed equally.

Abstract

Purpose: While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 μm) microspheres loaded with epirubicin.

Materials and methods: This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30-50), 75 (range, 60-90), or 100 (range, 75-125) μm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events.

Results: Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death.

Conclusion: DEB-TACE using epirubicin-loaded small-sized (≤ 100 μm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC.

Trial registration: Clinicaltrials.gov NCT03113955; registered April 14, 2017. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017.

Level of evidence: 2, Prospective, Non-randomized, Single-arm, study.

Keywords: Epirubicin; Hepatocellular carcinoma; TANDEM microspheres; Transarterial chemoembolization.

Publication types

Multicenter Study
Clinical Trial, Phase II

MeSH terms

Carcinoma, Hepatocellular* / pathology
Chemoembolization, Therapeutic* / methods
Doxorubicin
Epirubicin
Humans
Liver Neoplasms* / pathology
Microspheres
Prospective Studies
Retrospective Studies
Treatment Outcome

Substances

Epirubicin
Doxorubicin

Associated data

ClinicalTrials.gov/NCT03113955