Challenges of advanced hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials.

Keywords: Barcelona Clinic Liver Cancer; Portal vein thrombosis; Modified Response Evaluation Criteria in Solid Tumors; Advanced hepatocellular carcinoma management; Advanced hepatocellular carcinoma second line therapies; Sorafenib

Core tip: Hepatocellular carcinoma (HCC) is an aggressive malignancy, which accounts for great part of all cancer deaths each year. Its management is complex, and although the surveillance performed, many patients have an advanced stage. This comprehends an heterogeneous groups with different clinical condition; sorafenib is the only approved treatment, however affected by many adverse events. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Loco-regional therapies as TAE/TACE and TARE have also been tested and at now are under evaluation. This review will focus on patients with advanced HCC and highlights potential and limit of the therapies.