Usefulness of atezolizumab plus bevacizumab as second-line therapy for patients with unresectable hepatocellular carcinoma

PLoS One. 2024 Apr 30;19(4):e0298770. doi: 10.1371/journal.pone.0298770. eCollection 2024.

Abstract

Aim: To clarify the efficacy of atezolizumab (ATZ) plus bevacizumab (BEV) as the second-line therapy for patients with unresectable hepatocellular carcinoma (HCC).

Methods: The subjects were 82 patients with HCC receiving ATZ/BEV, including 33 patients with previous therapies with molecular-targeted agents (MTA). Therapeutic efficacy was evaluated using contrast-enhanced CT according to the mRECIST.

Results: The Child-Pugh scores were 5, 6,7 and 8 in 40, 35, 5 and 2 patients, respectively, and the extents of HCC progression were BCLC stage A, B and C in 3, 31 and 48 patients, respectively. Early therapeutic efficacy was evaluated in 67 patients, and percentages of patients achieving CR/PR/SD/PD until 12 weeks were 3.0%/29.9%/49.3%/17.9%, respectively, indicating ORR of 32.8% and DCR of 82.1%, The ORR was higher in MTA-naïve patients (40.5%) than in those after discontinuation of lenvatinib due to PD (7.7%, P = 0.0410), while the DCR was equivalent between both patients (83.3% vs 80.0%, P = 0.1184), and the multivariate analysis revealed previous MTA therapies with lenvatinib alone as a factor to deteriorate the ORR (HR of 4.846 (P = 0.0619)). The OS rates at 24 and 48 weeks were 86% and 72%, respectively, and the rates did not differ between MTA-naïve and MTA-experienced patients. Multivariate analyses revealed that achievement of CR, PR or SD and peripheral neutrophil/lymphocyte ratio were associated with a favorable outcome (HR of 0.124, P<0.0001 and 0.351, P = 0.0303).

Conclusions: ATZ/BEV merits consideration even for MTA-experienced patients, since the OS was equivalent to those in MTA-naïve patients despite of an unfavorable early therapeutic efficacy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Bevacizumab* / administration & dosage
  • Bevacizumab* / therapeutic use
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / pathology
  • Female
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / pathology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Treatment Outcome

Substances

  • atezolizumab
  • Bevacizumab
  • Antibodies, Monoclonal, Humanized

Grants and funding

Satoshi MOCHIDA has received speaking fees or honoraria from AbbVie GK, Gilead Sciences Inc., Otsuka Pharmaceutical Co., Ltd., Toray Medical Co. Ltd., Eisai Co., Ltd., ASKA Pharmaceutical Co., Ltd., has received research grants from EPS Corporation, Gilead Sciences Inc., MSD K.K., intellim Corporation, and scholarship grants from AbbVie GK., EA Pharma Co. Ltd., Eisai Co., Ltd., Sumitomo Pharma Co., Ltd. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.