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Adjuvant immune checkpoint inhibitors associated with higher recurrence-free survival in postoperative hepatocellular carcinoma (PREVENT): a prospective, multicentric cohort study

  • Original Article―Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Adjuvant therapy may improve survival of patients with hepatocellular carcinoma (HCC) after curative resection. This study compared safety and efficacy outcomes between patients at high risk of recurrence who received different types of adjuvant therapy or no such therapy after hepatic resection for HCC.

Methods

Recurrence-free survival (RFS), overall survival, and adverse events were compared among patients who received adjuvant immune checkpoint inhibitors (ICIs) alone, ICIs with tyrosine kinase inhibitors (TKIs), or no adjuvant therapy between 13 March 2019 and 19 March 2022. This study was registered on ClinicalTrials.gov (NCT05221398).

Results

Of the 517 patients in final analysis, 432 (83.6%) received no adjuvant therapy, 53 (10.2%) received ICIs alone, and 32 (6.2%) received adjuvant ICIs and TKIs. During median follow-up of 34.0 months (IQR 27.8 to 41.6 months), RFS was significantly longer among patients who received either type of adjuvant therapy (25.2 months, 95%CI 16.4–34.0) than among those who received none (16.1 months, 95%CI 12.9–19.4), and this difference remained significant after propensity score matching (HR 0.52, 95%CI 0.35–0.76, P = 0.004). Overall survival was unaffected by either type of adjuvant therapy, while significant difference was observed between patients who received adjuvant therapy or not after propensity score matching (HR 0.31, 95%CI 0.17–0.59, P = 0.005). The rate of grade 3 or 4 adverse events was similar between the two types of adjuvant therapy.

Conclusions

ICIs alone or with TKIs may improve RFS of patients at high risk of HCC recurrence after curative resection.

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Data availability

Data available on request due to privacy/ethical restrictions.

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Funding

This work was supported by the Specific Research Project of Guangxi for Research Bases and Talents (GuiKe AD22035057), the National Natural Science Foundation of China (82060510 and 82260569), the Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education (GKE-ZZ202217), the Self-raised Scientific Research Fund of the Ministry of Health of Guangxi Province (Z20200923 and Z20191054), and Guangxi Undergraduate Training Program for Innovation and Entrepreneurship (S202310598205).

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Author notes

  1. Le Li, Pei-Sheng Wu, and Xiu-Mei Liang contributed equally to this work.

Authors and Affiliations

  1. Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, He Di Rd. #71, Nanning, 530021, China

    Le Li, Xiu-Mei Liang, Kang Chen, Guan-Lan Zhang, Rong-Rui Huo, Rong-Wei Xie, Shan Huang, Liang Ma & Jian-Hong Zhong

  2. Hepatobiliary Surgery Department, the First People’s Hospital of Qinzhou, Qinzhou, China

    Pei-Sheng Wu & Qi-Bin Su

  3. Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, China

    Jian-Hong Zhong

  4. Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, China

    Jian-Hong Zhong

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Contributions

J-HZ conceived the study; all authors participated in the acquisition of the data; X-ML, LL, P-SW, Q-BS, and G-LZ performed follow-up of the data; LL, KC LM, and J-HZ analyzed the data; LL and J-HZ drafted and revised the manuscript; all authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Liang Ma or Jian-Hong Zhong.

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Supplementary Information

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Supplementary file1 (DOCX 39 KB)

535_2023_2018_MOESM2_ESM.jpeg

Supplementary file2 Supplementary Figure 1: Albumin–bilirubin score in patients with or without adjuvant therapy at the time of recurrence (P=0.157) (JPEG 422 KB)

535_2023_2018_MOESM3_ESM.tif

Supplementary file3 Supplementary Figure 2: Forest plot of survival in patient subgroups after propensity score-matched, based on Cox regression. a, recurrence-free survival; b, overall survival. CI, confidence interval; HBsAg, hepatitis B virus surface antigen; HBV, hepatitis B virus (TIF 466 KB)

Supplementary file4 (TIF 450 KB)

535_2023_2018_MOESM5_ESM.tif

Supplementary file5 Supplementary Figure 3: Comparison of survival between all patients who received ICIs alone or with TKIs. A, recurrence-free survival; B, overall survival. HR, hazard ratio; ICI, immune checkpoint inhibitor; TKI, tyrosine kinase inhibitor (TIF 403 KB)

535_2023_2018_MOESM6_ESM.tif

Supplementary file6 Supplementary Figure 4: Comparison of survival between all patients with or without fatty liver disease who received adjuvant therapy. A, recurrence-free survival; B, overall survival. HR, hazard ratio; FLD, fatty liver disease (TIF 369 KB)

Supplementary file7 (XLSX 10 KB)

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Li, L., Wu, PS., Liang, XM. et al. Adjuvant immune checkpoint inhibitors associated with higher recurrence-free survival in postoperative hepatocellular carcinoma (PREVENT): a prospective, multicentric cohort study. J Gastroenterol 58, 1043–1054 (2023). https://doi.org/10.1007/s00535-023-02018-2

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