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Systemic treatment in patients with Child-Pugh B liver dysfunction and advanced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a major cause of death among patients with liver cirrhosis. The rise of immuno-oncology has revolutionized treatment for advanced HCC. However, most pivotal randomized controlled trials have excluded patients with moderate liver dysfunction (Child-Pugh-Turcotte B), despite the high incidence of liver disease in patients with HCC at the time of diagnosis. Overall survival in patients with HCC and moderate liver dysfunction treated with sorafenib has been found to be only approximately 3-5 months, underlining the need for improved treatment algorithms for this increasingly important subgroup of patients. In this review, we summarize available data on the treatment of patients with HCC and moderate liver dysfunction. Opportunities, as well as clinical challenges, are discussed in detail, highlighting potential changes to the therapeutic landscape.

 

Comments:

Hepatocellular carcinoma (HCC) is a type of liver cancer that often develops in individuals with liver cirrhosis, a condition characterized by liver damage and scarring. HCC is a leading cause of cancer-related deaths worldwide, and patients with moderate liver dysfunction (Child-Pugh-Turcotte B) represent a substantial proportion of this population. Unfortunately, these patients have been excluded from many pivotal randomized controlled trials investigating novel therapies for advanced HCC.

The emergence of immuno-oncology has led to significant advances in the treatment of advanced HCC, particularly in patients with preserved liver function (Child-Pugh-Turcotte A). However, the efficacy of these therapies in patients with moderate liver dysfunction remains uncertain. Several studies have evaluated the use of sorafenib, a targeted therapy, in this patient population, with disappointing results.

The limited efficacy of sorafenib in patients with HCC and moderate liver dysfunction underscores the need for improved treatment algorithms for this subgroup of patients. One potential strategy is to identify patients with the highest likelihood of benefiting from available therapies based on biomarkers and clinical characteristics. Another approach is to develop novel therapies specifically designed for patients with compromised liver function, such as those targeting immune checkpoints or liver regeneration pathways.

Clinical challenges in the management of HCC and moderate liver dysfunction include the risk of adverse events associated with systemic therapies, the need for frequent monitoring of liver function, and the potential for drug interactions with concomitant medications used to manage liver disease. These challenges highlight the importance of a multidisciplinary approach to the care of patients with HCC, involving specialists in oncology, hepatology, and other relevant fields.

In conclusion, the management of HCC and moderate liver dysfunction remains an area of significant unmet need. Advances in biomarker identification and targeted therapy development hold promise for improving outcomes in this patient population. However, the complex interplay between liver function and cancer progression requires careful consideration in the design of clinical trials and treatment algorithms.

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S7397 Sorafenib Sorafenib is a multikinase inhibitor of Raf-1 and B-Raf with IC50 of 6 nM and 22 nM in cell-free assays, respectively. Sorafenib inhibits VEGFR-2, VEGFR-3, PDGFR-β, Flt-3 and c-KIT with IC50 of 90 nM, 20 nM, 57 nM, 59 nM and 68 nM, respectively. Sorafenib induces autophagy and apoptosis and activates ferroptosis with anti-tumor activity.

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