Lessons From Immune Checkpoint Inhibitor Trials in Hepatocellular Carcinoma

Abstract

The implementation of immune checkpoint inhibitors (ICI) into the clinical management of different malignancies has largely changed our understanding of cancer treatment. After having proven efficacy in different tumor entities such as malignant melanoma and lung cancer, ICI were intensively tested in the setting of hepatocellular carcinoma (HCC). Here they could achieve higher and more durable response rates compared to tyrosine-kinase inhibitors (TKI), that were sole standard of care for the last decade. Most recently, ICI treatment was approved in a first line setting of HCC, for cases not suitable for curative strategies. However, only a subset of patients benefits from ICI therapy, while others experience rapid tumor progression, worsening of liver function and poor prognosis. Efforts are being made to find immune characteristics that predict tumor responsiveness to ICI, but no reliable biomarker could be identified so far. Nevertheless, data convincingly demonstrate that combination therapies (such as dual inhibition of PD-L1 and VEGF) are more effective than the application of single agents. In this review, we will briefly recapitulate the current algorithms for systemic treatment, discuss available results from checkpoint inhibitor trials and give an outlook on future directions of immunotherapy in HCC.

Infiltrative hepatocellular carcinoma with multiple lung metastasis completely cured using nivolumab: a case report

“…ICIs block the inhibitory immune checkpoints and ultimately trigger an immune response targeting tumor tissue. 11,12 Multiple ongoing phase I-III clinical trials are evaluating ICI monotherapy for the treatment of advanced HCC. 13,14 Several clinical studies are evaluating nivolumab as monotherapy and combination therapy for advanced HCC.…”

Targets of immunotherapy for hepatocellular carcinoma: An update

“…Immune check-point inhibitor therapy has been approved as first-line therapy in the cases not suitable for surgery and has been proven beneficial in stabilizing the quality of life, however, only a subset of patients has shown positive outcome and there are reports of tumor progression, worsening of liver function, and poor prognosis in others. The reason behind the equivocal results in clinical trials for immune check-point inhibitor therapy is due to the lack of biomarkers to check the tumor responsiveness during therapy[ 41 ]. Different strategies to assess the response and cut off values for the biomarkers are another reason for failure of immune check-point inhibitor therapy[ 42 ].…”

Inhibidores tirosín quinasa en el tratamiento del hepato-carcinoma avanzado

“…Actualmente, los fármacos inmunoterápicos de segunda línea para el tratamiento de CHC se encuentran en fases de prueba en ensayos clínicos (Mohr et al, 2021).…”