Lenvatinib combined with anti-PD-1 antibodies plus locoregional treatment for initial unresectable hepatocellular carcinoma with portal vein tumor thrombosis: a multicenter real-world study

BMC Cancer. 2025 Jul 10;25(1):1162. doi: 10.1186/s12885-025-14543-9.

Abstract

Background: Unresectable hepatocellular carcinoma (uHCC) with portal vein tumor thrombosis (PVTT) has poor prognoses. This study evaluated the efficacy and safety of lenvatinib (LEN) combined with anti-PD-1 antibodies (PD-1) and locoregional therapy (LRT) in uHCC patients with PVTT.

Methods: Consecutive uHCC patients with PVTT who received LEN, PD-1, and LRT (LPLRT), such as transcatheter arterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), or TACE-HAIC, were analyzed. Objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (TRAEs) were assessed. Subgroup analysis and multivariate Cox regression analysis was performed to identify independent risk factors for OS and PFS.

Results: Between January 2019 and December 2021, 74 uHCC patients with PVTT at four tertiary hospitals were enrolled. Of these, 38 were treated with LEN, PD-1, and TACE (LPT), 12 with LEN, PD-1, and HAIC (LPH), and 24 with LEN, PD-1, and TACE-HAIC (LPTH). According to the modified Response Evaluation Criteria in Solid Tumors, the ORR and DCR were 62.1% and 85.1%, respectively. The median OS was 23.3 months (95% CI, 18.9-27.7 months), and the median PFS was 13.2 months (95% CI, 8.8-17.6 months). Subgroup analyses revealed no significant differences in ORR, DCR, OS or PFS among the LPT, LPH, and LPTH groups. No grade 5 TRAEs occurred. Twenty-nine patients underwent salvage surgery. Significant differences in OS and PFS rates were observed between the resection and non-resection groups (p < 0.001 for both). Multivariate analysis showed that surgical resection was an independent prognostic factor for OS and PFS.

Conclusion: LPLRT therapy offers a promising treatment for uHCC patients with PVTT, demonstrating high tumor response and conversion rates, prolonged survival, and manageable safety. Notably, for patients who remain eligible for surgery following LPLRT, salvage surgery is a safe, effective, and potentially prognostic treatment option.

Keywords: Locoregional therapy; Portal vein tumor thrombosis; Surgery; Systemic therapy; Unresectable hepatocellular carcinoma.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Carcinoma, Hepatocellular* / complications
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / mortality
  • Carcinoma, Hepatocellular* / pathology
  • Carcinoma, Hepatocellular* / therapy
  • Chemoembolization, Therapeutic / methods
  • Combined Modality Therapy
  • Female
  • Humans
  • Immune Checkpoint Inhibitors* / administration & dosage
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Liver Neoplasms* / complications
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / pathology
  • Liver Neoplasms* / therapy
  • Male
  • Middle Aged
  • Phenylurea Compounds* / administration & dosage
  • Phenylurea Compounds* / adverse effects
  • Phenylurea Compounds* / therapeutic use
  • Portal Vein* / pathology
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Quinolines* / administration & dosage
  • Quinolines* / therapeutic use
  • Retrospective Studies
  • Venous Thrombosis* / etiology
  • Venous Thrombosis* / therapy

Substances

  • lenvatinib
  • Phenylurea Compounds
  • Quinolines
  • Programmed Cell Death 1 Receptor
  • PDCD1 protein, human
  • Immune Checkpoint Inhibitors