Intensity-modulated radiotherapy combined with systemic atezolizumab and bevacizumab in treatment of hepatocellular carcinoma with extrahepatic portal vein tumor thrombus: A preliminary multicenter single-arm prospective study

Front Immunol. 2023 Feb 16:14:1107542. doi: 10.3389/fimmu.2023.1107542. eCollection 2023.

Abstract

Background and aims: The efficacy and safety of systemic atezolizumab and bevacizumab (atezo/bev) in treatment of patients with unresectable hepatocellular carcinoma (HCC) have been demonstrated. However, the efficacy of this treatment in patients with HCC and extrahepatic portal vein tumor thrombus (ePVTT) is not satisfactory. This study aimed to study the efficacy and safety of combining intensity-modulated radiotherapy (IMRT) with systemic atezo/bev in treatment of these patients.

Methods: This multicenter prospective study included patients with ePVTT treated with IMRT combined with atezo/bev from March to September 2021 in three centers in China. The outcomes of this study included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), time to progression (TTP), and association between response and tumor mutational burden (TMB). Treatment-related adverse events (TRAEs) were analyzed to assess safety.

Results: Of 30 patients in this study, the median follow-up was 7.4 months. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, the ORR was 76.6%, the median OS for the entire cohort was 9.8 months, the median PFS was 8.0 months, and the median TTP was not reached. This study failed to establish a significant correlation between TMB with any of the following outcomes, including ORR, OS, PFS or TTP. The most common TRAEs at all levels were neutropenia (46.7%), and the most common grade 3/4 TRAE was hypertension (16.7%). There was no treatment-related deaths.

Conclusions: IMRT combined with atezo/bev showed encouraging treatment efficacy with an acceptable safety profile, making this treatment to be a promising option for HCC patients with ePVTT. Further studies are required to support the findings of this preliminary study.

Clinical trial registration: http://www.chictr.org.cn, Identifier ChiCTR2200061793.

Keywords: PD-L1 inhibitor; combination therapy; immunotherapy; intensity-modulated radiotherapy; macrovascular invasion.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bevacizumab
  • Carcinoma, Hepatocellular*
  • Humans
  • Liver Neoplasms*
  • Neutropenia*
  • Portal Vein
  • Prospective Studies
  • Radiotherapy, Intensity-Modulated*

Substances

  • Bevacizumab
  • atezolizumab

Grants and funding

This work was supported by the Clinical Research Plan of Shanghai Hospital Development Center (SHDC2020CR1004A), the Key Project of the National Natural Science Foundation of China (81730097), the National Natural Science Foundation of China (82072618), and the National Key Research and Development Program of China (2022YFC2503700).