Whole genome/exome and RNA sequencing guided therapy is feasible in patients with hepatocellular carcinoma (HCC) and hepatocholangiocarcinoma (hepato CCA) refractory to atezolizumab/bevacizumab treatment, according to a new study published in the Journal of Hepatology.
The approach “may be useful in a small subset of patients,” the authors noted. “This approach will be required in a larger cohort of patients,” they added.
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Whole genome/exome and RNA sequencing have never been used in patients with HCC and hepato CCA in clinical practice before.
The study team analyzed 135 patients with HCC and hepato CCA whose disease progressed under atezolizumab/bevacizumab treatment. Frozen tumor samples were available for all patients.
Of the 135 patients, 20 benefited from genomic analysis after progression. Of these, 16 had HCC, and 4 had hepato CCA. Of the 19 patients with data available for analysis, 65% had metastatic disease, and 45% had vascular invasion.
The majority of patients (76%) harbored at least 1 actionable genomic alteration, 9 of which was treated with an adapted targeted therapy.
One patient with hepato CCA with CDK4 amplification received treatment with palbociclib and had a partial radiological response for 16 months.
Another patient with the disease with HER2 overexpression and a high homologous recombination score was given trastuzumab/olaparib and had stable disease.
One patient with HCC who had biallelic inactivation of TSC2, silencing its gene expression, had a complete radiological response to everolimus treatment.
The remaining 6 treated patients with HCC who were treated had progressive disease. Of these, 3 were treated with trametinib, 2 with everolimus, and 1 with olaparib.
“This is a proof-of-concept study suggesting that a small subset of patients have a clinical benefit from this strategy,” the researchers concluded.
Reference
Limousin W, Laurent-Puig P, Ziol M, et al. Molecular-based targeted therapies in patients with hepatocellular carcinoma and hepato-cholangiocarcinoma refractory to atezolizumab/bevacizumab. J Hepatol. Published online August 28, 2023. doi:10.1016/j.jhep.2023.08.017
