Stereotactic Body Radiotherapy Combined With Lenvatinib With or Without PD-1 Inhibitors as Initial Treatment for Unresectable Hepatocellular Carcinoma

Int J Radiat Oncol Biol Phys. 2024 Dec 1;120(5):1363-1376. doi: 10.1016/j.ijrobp.2024.03.035. Epub 2024 Apr 6.

Abstract

Purpose: The aim of this study was to compare the clinical benefit and safety of the triple combination of stereotactic body radiotherapy (SBRT), lenvatinib, and programmed cell death protein 1 (PD-1) inhibitors with the dual combination of SBRT and lenvatinib in patients with unresectable hepatocellular carcinoma (uHCC).

Methods and materials: Patients with uHCC who received SBRT in combination with lenvatinib and PD-1 inhibitors or SBRT in combination with lenvatinib alone as first-line treatment from October 2018 to July 2022 were reviewed in this study. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints were intrahepatic PFS, extrahepatic PFS, and objective remission rate. In addition, safety profiles were assessed by analyzing treatment-related adverse events between the two groups to assess safety profiles.

Results: In total, 214 patients with uHCC who received combination therapy were included in this retrospective study. Among them, 146 patients received triple combination therapy of SBRT, lenvatinib, and PD-1 inhibitors (SBRT-L-P group), and 68 patients received dual therapy of SBRT and lenvatinib (SBRT-L group). The median OS times of the 2 groups were 31.2 months and 17.4 months, respectively (P < .001). The median PFS time was significantly longer in the SBRT-L-P group than in the SBRT-L group (15.6 months vs 8.8 months, P < .001). Additionally, the median intrahepatic PFS (17.5 vs 9.9 months, P < .001) and extrahepatic PFS (20.9 vs 11.6 months, P < .001) were significantly longer in the SBRT-L-P group than in the SBRT-L group. The objective remission rate in the SBRT-L-P group was higher than in the SBRT-L group (63.0 vs 39.7%, P = .002). The incidence and severity of treatment-related adverse events in the SBRT-L-P group were comparable to those in the SBRT-L group.

Conclusion: The use of both lenvatinib and PD-1 inhibitors with SBRT in patients with uHCC was associated with improved overall survival compared with lenvatinib and SBRT alone with a manageable safety profile.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / mortality
  • Carcinoma, Hepatocellular* / therapy
  • Combined Modality Therapy
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / therapy
  • Male
  • Middle Aged
  • Phenylurea Compounds* / therapeutic use
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Progression-Free Survival
  • Quinolines* / therapeutic use
  • Radiosurgery* / adverse effects
  • Radiosurgery* / methods
  • Retrospective Studies

Substances

  • lenvatinib
  • Phenylurea Compounds
  • Quinolines
  • Programmed Cell Death 1 Receptor
  • Immune Checkpoint Inhibitors