Serum interleukin-6 levels at the start of the second course of atezolizumab plus bevacizumab therapy predict therapeutic efficacy in patients with advanced hepatocellular carcinoma: a multicenter analysis

J Gastroenterol Hepatol. 2024 Oct;39(10):2158-2168. doi: 10.1111/jgh.16672. Epub 2024 Jun 28.

Abstract

Background and aim: Serum interleukin-6 (IL-6) before the administration of atezolizumab plus bevacizumab (Atez + Bev) is a prognostic biomarker in patients with hepatocellular carcinoma (HCC) treated with Atez + Bev. We previously revealed that the neutrophil-to-lymphocyte ratio and serum chemokine levels during treatment with Atez + Bev were more useful as prognostic biomarkers. Therefore, we examined the predictive ability of serum IL-6 for the efficacy of Atez + Bev in patients with HCC.

Methods: We enrolled 94 patients with HCC who received treatment with Atez + Bev. Initial responses were assessed through dynamic computed tomography or magnetic resonance imaging. The levels of IL-6 in serum were measured before and at the initiation of the second course of Atez + Bev. Subsequently, the relationship of IL-6 levels with treatment efficacy was evaluated.

Results: IL-6 levels at the initiation of the second course tended to be higher in patients with progressive disease versus those with non-progressive disease in the initial evaluation (P = 0.054). Moreover, the cutoff value (7.4 pg/mL) was useful in stratifying patients by overall survival (i.e. low vs high: not reached vs 21.4 months, respectively, P = 0.001) and progression-free survival (low vs high: 11.9 vs 5.2 months, respectively, P = 0.004). This result was reproduced in patients with HCC who received Atez + Bev as first-line therapy. In the multivariate analyses, IL-6 levels at the initiation of the second course were independent predictive factors for progression-free and overall survival.

Conclusions: Serum levels of IL-6 at the initiation of the second course of treatment may predict Atez + Bev efficacy and prognosis in HCC.

Keywords: atezolizumab; bevacizumab; cytokine; hepatocellular carcinoma; interleukin‐6.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Bevacizumab* / administration & dosage
  • Biomarkers, Tumor / blood
  • Carcinoma, Hepatocellular* / blood
  • Carcinoma, Hepatocellular* / diagnostic imaging
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / mortality
  • Female
  • Humans
  • Interleukin-6* / blood
  • Liver Neoplasms* / blood
  • Liver Neoplasms* / diagnostic imaging
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / mortality
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Treatment Outcome

Substances

  • Interleukin-6
  • atezolizumab
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Biomarkers, Tumor
  • IL6 protein, human