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

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....

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Published in:Cancers 2020-12, Vol.12 (12), p.3830
Main Authors: Spahn, Stephan, Roessler, Daniel, Pompilia, Radu, Gabernet, Gisela, Gladstone, Beryl Primrose, Horger, Marius, Biskup, Saskia, Feldhahn, Magdalena, Nahnsen, Sven, Hilke, Franz J, Scheiner, Bernhard, Dufour, Jean-François, De Toni, Enrico N, Pinter, Matthias, Malek, Nisar P, Bitzer, Michael
Format: Article
Language:English
Subjects:
Antibiotics
Antibodies
Cancer therapies
FDA approval
Hepatocellular carcinoma
Immune checkpoint inhibitors
Immunotherapy
Liver cancer
Liver cirrhosis
Microbiomes
Mutation
Next-generation sequencing
Patients
PD-1 protein
Tumors
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Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers12123830