Clinical and Genetic Tumor Characteristics of Responding and Non-Responding Patients to PD-1 Inhibition in Hepatocellular Carcinoma

Cancers

Magdalena Feldhahn¹  Saskia Biskup¹  BerylPrimrose Gladstone²  Stephan Spahn²  Michael Bitzer²  NisarP. Malek²  Marius Horger³  EnricoN. De Toni⁴  Daniel Roessler⁴  Bernhard Scheiner⁵  Matthias Pinter⁵  Jean-François Dufour⁶  Radu Pompilia⁶  FranzJ. Hilke⁷  Sven Nahnsen⁸  Gisela Gabernet⁸ 

[1] CeGaT GmbH and Praxis für Humangenetik, 72076 Tuebingen, Germany;Department Internal Medicine I, Eberhard-Karls University, 72076 Tuebingen, Germany;Department of Diagnostic and Interventional Radiology, Eberhard-Karls University, 72076 Tuebingen, Germany;Department of Medicine II, University Hospital Ludwig-Maximilians-University (LMU), 81377 Munich, Germany;Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria;Hepatology-Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland;Institute of Medical Genetics and Applied Genomics, Eberhard-Karls University, 72076 Tuebingen, Germany;Quantitative Biology Center (QBiC), Eberhard-Karls University, 72076 Tuebingen, Germany;

关键词: hepatocellular carcinoma;    immunotherapy;    biomarkers;    microbiome;    tumor mutational burden;   

DOI  :  10.3390/cancers12123830

来源: DOAJ

【 摘 要 】

Immune checkpoint inhibitors (ICIs) belong to the therapeutic armamentarium in advanced hepatocellular carcinoma (HCC). However, only a minority of patients benefit from immunotherapy. Therefore, we aimed to identify indicators of therapy response. This multicenter analysis included 99 HCC patients. Progression-free (PFS) and overall survival (OS) were studied by Kaplan-Meier analyses for clinical parameters using weighted log-rank testing. Next-generation sequencing (NGS) was performed in a subset of 15 patients. The objective response (OR) rate was 19% median OS (mOS)16.7 months. Forty-one percent reached a PFS > 6 months; these patients had a significantly longer mOS (32.0 vs. 8.5 months). Child-Pugh (CP) A and B patients showed a mOS of 22.1 and 12.1 months, respectively. Ten of thirty CP-B patients reached PFS > 6 months, including 3 patients with an OR. Tumor mutational burden (TMB) could not predict responders. Of note, antibiotic treatment within 30 days around ICI initiation was associated with significantly shorter mOS (8.5 vs. 17.4 months). Taken together, this study shows favorable outcomes for OS with low AFP, OR, and PFS > 6 months. No specific genetic pattern, including TMB, could identify responders. Antibiotics around treatment initiation were associated with worse outcome, suggesting an influence of the host microbiome on therapy success.

【 授权许可】

Unknown