Scientific Reports (Aug 2024)

Impact of metformin, statin, aspirin and insulin on the prognosis of uHCC patients receiving first line Lenvatinib or Atezolizumab plus Bevacizumab

  • Margherita Rimini,
  • Margarida Montes,
  • Elisabeth Amadeo,
  • Francesco Vitiello,
  • Masatoshi Kudo,
  • Toshifumi Tada,
  • Goki Suda,
  • Shigeo Shimose,
  • Sara Lonardi,
  • Fabian Finkelmeier,
  • Francesca Salani,
  • Lorenzo Antonuzzo,
  • Fabio Marra,
  • Massimo Iavarone,
  • Giuseppe Cabibbo,
  • Francesco Giuseppe Foschi,
  • Marianna Silletta,
  • Rodolfo Sacco,
  • Ilario Giovanni Rapposelli,
  • Mario Scartozzi,
  • Pella Nicoletta,
  • Luca Aldrighetti,
  • Mara Persano,
  • Silvia Camera,
  • Federico Rossari,
  • Silvia Foti,
  • Takashi Kumada,
  • Atsushi Hiraoka,
  • Hideki Iwamoto,
  • Mario Domenico Rizzato,
  • Vera Himmelsbach,
  • Gianluca Masi,
  • Mattia Corradi,
  • Ciro Celsa,
  • Conti Fabio,
  • Giovanni Luca Frassineti,
  • Stefano Cascinu,
  • Andrea Casadei-Gardini,
  • Jose Presa

DOI
https://doi.org/10.1038/s41598-024-70928-z
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 14

Abstract

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Abstract Recently, in Hepatocellular carcinoma (HCC) setting, the use of metformin has been associated to a trend toward worse response rate, overall survival and progression free survival in patients who received immunotherapy. The study population included individuals from both Eastern and Western regions with a confirmed diagnosis of HCC and receiving first line treatment with Atezolizumab plus bevacizumab or Lenvatinib. Univariate and multivariate analyses were performed by Cox proportional. For the analysis, patients were stratified based on their use of concomitant medication or not. At the time of database lock, 319 deaths were observed: 209 in the Lenvatinib cohort, 110 in the Atezolizumab plus bevacizumab cohort. In the Atezolizumab plus Bevacizumab arm, 50 (16.5%) patients were on chronic metformin use. At the univariate analysis for OS, patients who used metformin showed significantly shorter OS compared to patients who did not use metformin (HR 1.9, 95% CI 1.1–3.2). Multivariate analysis confirmed that patients in metformin group had significantly shorter OS compared to patients in no-metformin group (HR 1.9; 95% CI 1.1–3.1). At the univariate analysis for PFS, patients in metformin group had significantly shorter PFS compared to patients in no-metformin group (HR 1.6, 95% CI 1.0–2.6). Multivariate analysis confirmed that patients in metformin group had significantly shorter PFS compared to patients in no-metformin group (HR 1.7; 95% CI 1.1–2.7; p = 0.0147). No differences were reported in terms of ORR and DCR between patients in metformin group and those in no-metformin group. In the Lenvatinib cohort, 65 (15%) patients were recorded to chronically use metformin. No statistically significant differences in terms of both OS and PFS were found between patients in metformin group and patients in no-metformin group. This analysis unveils a negative prognostic role associated with metformin use specifically within the Atezolizumab plus Bevacizumab group.

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