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Immunotherapy for Advanced Hepatocellular Carcinoma-a Large Tertiary Center Experience

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Journal of Gastrointestinal Surgery

Abstract

Introduction

Combination of immune-checkpoint inhibitor (ICI) and vascular endothelial growth factor (VEGF) antagonist has become the first line systemic treatment for advanced hepatocellular carcinoma (HCC). However, two-thirds of patients do not respond to ICI-based treatments and biomarkers for response remain elusive.

Methods

Patients with advanced HCC who received Atezolizumab/Bevacizumab combination or Nivolumab during 2016-2022 were identified in our Liver Cancer Database. Retrospective review of their clinical data was performed to investigate parameters that could be predictive of immunotherapy response.

Results

96 patients received Atezolizumab/Bevacizumab (n=60) or Nivolumab (n=36). Median age at diagnosis was 67.1 years. 70 patients had received treatment and 26 patients were treatment naïve before starting immunotherapy. Mean pre-treatment AFP was 9780.7 (±32035) ng/mL. Confirmed objective response (complete or partial) was seen in 29% of the population (n=27). Disease remained stable in 12% (n=11) and progressed in 60% (n=56). On univariate analysis, pre-treatment AFP>400 ng/mL was associated with objective response (OR=4.5, 95% CI:1.7-11.9, p=0.0015), while white race (OR=0.35, 95% CI:0.13-0.92, p=0.030) and prior radiotherapy (OR=0.14, 95% CI:0.01-1.1, p=0.033) or systemic therapy with TKIs (OR=0.25, 95% CI:0.08-0.81, p=0.017) were associated with poor response. On multivariate analysis only AFP>400 ng/mL remained associated with response (OR=3.7, 95% CI:1.3-10.5, p=0.014). Overall survival (OS) at one and three years was 86% and 43% in responders, and 45% and 29% in non-responders, respectively.

Conclusion

In our institutional experience, treatment naivety and pre-treatment AFP>400 ng/mL were associated with objective response. Prospective studies aimed at identifying factors associated with response to immunotherapy will aide patient selection.

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Authors and Affiliations

  1. Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Department of Hepato-pancreato-biliary & Liver Transplant Surgery, OH, Cleveland, USA

    Roma Raj MD, Nihal Aykun MD, Chase J. Wehrle MD, Marianna Maspero MD & Federico Aucejo MD

  2. Cleveland Clinic Foundation, Taussig Cancer Institute, Department of Hematology and Oncology, Cleveland, OH, USA

    Smitha Krishnamurthi MD, Bassam Estfan MD & Suneel Kamath MD

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  1. Roma Raj MD
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  2. Nihal Aykun MD
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Contributions

The study was conceptualized and conducted under the direction of Dr. Federico Aucejo by RR and NA. Data was collected by RR, NA, and CW. Data was analyzed by RR, MM, NA, CW, SK, BE, and FA. BE, SK and SK provided direction of the medical oncology interpretation of results and placed into context of systemic therapy. The manuscript was written by RR, BE, SK, SK, and FA. The manuscript was reviewed and critically approved by RR, NA, CW, MM, SK, BE, SK, and FA.

Corresponding authors

Correspondence to Roma Raj MD or Federico Aucejo MD.

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This work was presented in the Plenary Session at the Society for Surgery of the Alimentary Tract (SSAT) Annual Meeting/Digestive Diseases Week on May 9th, 2023 in Chicago.

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Raj, R., Aykun, N., Wehrle, C.J. et al. Immunotherapy for Advanced Hepatocellular Carcinoma-a Large Tertiary Center Experience. J Gastrointest Surg 27, 2126–2134 (2023). https://doi.org/10.1007/s11605-023-05783-w

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