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Cited by 136Hepatocellular Carcinoma Treatment and PrognosisCancer Immunotherapy and BiomarkersColorectal Cancer Treatments and Studies

Lenvatinib plus anti-PD-1 antibodies as conversion therapy for patients with unresectable intermediate-advanced hepatocellular carcinoma: a single-arm, phase II trial

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Zhang, Wenwen, Tong, Shuang, Hu, Bingyang, Wan, Tao, Tang, Haowen, Zhao, Feilong, Jiao, Tianyu, Li, Junfeng +17 more·2023·Journal for ImmunoTherapy of Cancer
DOI 10.1136/jitc-2023-007366PMC PMC10514649
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Abstract

Background: Over 70% of the patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage and lose the opportunity for radical surgery. Combination therapy of tyrosine kinase inhibitors (TKIs) and anti-programmed cell death protein-1 (PD-1) antibodies has achieved a high tumor response rate in both the first-line and second-line treatment of advanced HCC. However, few studies have prospectively evaluated whether TKIs plus anti-PD-1 antibodies could convert unresectable intermediate-advanced HCC into resectable disease. Methods: This single-arm, phase II study enrolled systemic therapy-naïve adult patients with unresectable Barcelona Clinic Liver Cancer stage B or C HCC. Patients received oral lenvatinib one time per day plus intravenous anti-PD-1 agents every 3 weeks (one cycle). Tumor response and resectability were evaluated before the fourth cycle, then every two cycles. The primary endpoint was conversion success rate by investigator assessment. Secondary endpoints included objective response rate (ORR) by independent imaging review (IIR) assessment per modified RECIST (mRECIST) and Response Evaluation Criteria in Solid Tumors, V.1.1 (RECIST 1.1), progression-free survival (PFS) and 12-month recurrence-free survival (RFS) rate by IIR per mRECIST, R0 resection rate, overall survival (OS), and safety. Biomarkers were assessed as exploratory objectives. Results: Of the 56 eligible patients enrolled, 53 (94.6%) had macrovascular invasion, and 16 (28.6%) had extrahepatic metastasis. The median follow-up was 23.5 months. The primary endpoint showed a conversion success rate of 55.4% (31/56). ORR was 53.6% per mRECIST and 44.6% per RECIST 1.1. Median PFS was 8.9 months, and median OS was 23.9 months. Among the 31 successful conversion patients, 21 underwent surgery with an R0 resection rate of 85.7%, a pathological complete response rate of 38.1%, and a 12-month RFS rate of 47.6%. Grade ≥3 treatment-related adverse events were observed in 42.9% of patients. Tumor immune microenvironment analysis of pretreatment samples displayed significant enrichment of CD8+ T cells (p=0.03) in responders versus non-responders. Conclusion: Lenvatinib plus anti-PD-1 antibodies demonstrate promising efficacy and tolerable safety as conversion therapy in unresectable HCC. Pre-existing CD8+ cells are identified as a promising biomarker for response to this regimen. Trial registration number: Chinese Clinical Trial Registry, ChiCTR1900023914.

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  • The combination of anti-PD-1 and lenvatinib raises the HCC patient response rate from 17% with anti-PD-1 alone to 45%.

    “The combination of anti-PD-1 and lenvatinib, a multi-target tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF) receptors, raises the HCC patient response rate from 17% with anti-PD-1 alone to 45%.”

    From Contrasting cytotoxic and regulatory T cell responses underlying distinct clinical outcomes to anti-PD-1 plus lenvatinib therapy in cancer (2025) · cites this paper as [16]

    The Results (Response and conversion to resection; page unavailable) report a 44.6% response rate by RECIST 1.1 for lenvatinib plus anti-PD-1 antibodies, supporting the rounded 45% figure. The study was single-arm: our copy does not report a 17% anti-PD-1-alone response rate or establish that adding lenvatinib raised the rate from 17% to 45%. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Pre-treatment CD8+ T cell presence is linked to responses to ICB and anti-PD-1 plus lenvatinib in HCC patients.

    “Pre-treatment CD8+ T cell presence is linked to responses to ICB and anti-PD-1 plus lenvatinib in HCC patients.”

    From Contrasting cytotoxic and regulatory T cell responses underlying distinct clinical outcomes to anti-PD-1 plus lenvatinib therapy in cancer (2025) · cites this paper as [16]

    The Discussion reports that pretreatment CD8+ T cells were significantly more abundant in HCC tumors responding to lenvatinib plus anti-PD-1 therapy. It also links CD8+ cells to anti-PD-1/L1 response through previous studies across multiple tumor types, but does not establish a separate ICB-response association specifically in HCC patients. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

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Authors
Zhang, W., Tong, S., Hu, B., Wan, T., Tang, H., Zhao, F., Jiao, T., Li, J., Zhang, Z., Cai, J., Ye, H., Wang, Z., Chen, S., Wang, Y., Li, X., Wang, F., Cao, J., Tian, L., Zhao, X., Chen, M., Wang, H., Cai, S., Hu, M., Bai, Y., & Lu, S.
Affiliations
  • Chinese PLA General Hospital (CN)
  • 3D Medicines, Inc. (China) (CN)
  • Affiliated Hospital of Qingdao University (CN)
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
  • Peking University Cancer Hospital (CN)
Corresponding author
Lu, Shichun
ORCID
Venue
Journal for ImmunoTherapy of Cancer
Publisher
BMJ
Published
2023-09
Volume
11
Issue
9
Pages
e007366
ISSN
2051-1426 (ISSN-L)
DOI
10.1136/jitc-2023-007366
PMC
PMC10514649
OpenAlex
W4386898500
Cited by
136
References
1
Citations by year
2026: 34 · 2025: 61 · 2024: 40 · 2023: 1
FWCI
22.77
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal for ImmunoTherapy of Cancer (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Keywords
lenvatinib, anti-PD-1, hepatocellular carcinoma, conversion therapy, tyrosine kinase inhibitors, immune checkpoint inhibitors, resectability, R0 resection, tumor immune microenvironment, PD-L1 expression, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, prognostic factors
MeSH terms
Adult, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Phenylurea Compounds, Quinolines, CD8-Positive T-Lymphocytes, Tumor Microenvironment

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