Recent advances in medical management of hepatocellular carcinoma

Abstract

Transcatheter arterial therapies for hepatocellular carcinoma (HCC) have developed during the last decade. A fine powder formulation of cisplatin and the new platinum agent miriplatin became standard medicines in addition to anthracyclines in transcatheter arterial chemoembolization (TACE) in Japan. Recent prospective and retrospective studies supported the usefulness of platinum agents as a chemotherapeutic at the time of varied TACE therapy. Although balloon-occluded TACE is an effective therapy for localized HCC and drug-eluting microspheres seemed to show a higher response rate in certain HCCs, the definite advantages of those procedures still remain uncertain. Intermediate stage HCC, or Barcelona Clinic Liver Cancer stage B, is regarded as a heterogeneous category with a wide spectrum of tumors and patients, and several subclassifications of the stage have been proposed to show different prognoses; there are also different recommended therapies in each subgroup. Authors have subclassified patients based on combinations of tumor size, tumor number, and liver function, with or without performance status. Because of differences of available medical resources and techniques in treatment procedures between countries, the most ideal and useful subgrouping remains inconclusive at present. Recently, a few systemic chemotherapies proved to be effective for advanced stage HCC in phase III studies: lenvatinib as the first line of therapy, and regorafenib, cabozantinib, and ramucirumab as second-line therapy. Other molecular-targeted and immune-oncological medicines are expected to follow in the near future. Some studies have suggested an advantage of early introduction of moleculartargeted therapy for TACE-resistant HCC in the intermediate stage.

Clinical characteristics and outcomes of candidates for second‐line therapy, including regorafenib and ramucirumab, for advanced hepatocellular carcinoma after sorafenib treatment

“…In the near future, several other promising second‐line agents, such as cabozantinib, ramucirumab, nivolumab, and pembrolizumab, will become available in the clinical setting for patients refractory or intolerant to sorafenib. The post‐progression survival (PPS) of patients who are refractory or intolerant to sorafenib is expected to improve by switching from sorafenib to second‐line therapy …”

“…The post-progression survival (PPS) of patients who are refractory or intolerant to sorafenib is expected to improve by switching from sorafenib to second-line therapy. [7][8][9] However, not all patients who are refractory or intolerant to sorafenib can be switched to second-line therapy. [10][11][12][13][14] Because the efficacy and safety of regorafenib in patients who do not meet the eligibility criteria for the RESORCE trial have not been verified, the Japan Clinical Practice Guidelines for Hepatocellular Carcinoma 2017 and the Barcelona Clinic Liver Cancer (BCLC) Guidelines for Hepatocellular Carcinoma 2018 recommended regorafenib as second-line treatment for patients tolerant to sorafenib and well-preserved liver function (Child-Pugh A) after radiologic PD with sorafenib.…”

Prognostic impact of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation in patients with unresectable hepatocellular carcinoma: Comparison with TACE alone using decision‐tree analysis after propensity score matching

“…Transcatheter arterial chemoembolization (TACE) is a standard therapy for unresectable HCC, especially for patients with BCLC B . Several studies have shown that TACE significantly improves patient survival compared to the best supportive care and can prolong survival in patients with multiple HCC tumors and no macrovascular invasion .…”

Role of cyclin‐dependent kinases (CDKs) in hepatocellular carcinoma: Therapeutic potential of targeting the CDK signaling pathway

“…However, clinically, sorafenib has either not significantly increased survival or only increased survival by 2.8 months in advanced HCC patients . More recently, some new TKI drugs have been reported to be effective for advanced stage HCC in phase III studies: lenvatinib as the first line of therapy, and regorafenib as second‐line therapy . As a current research hotspot, blockade of cytotoxic T lymphocyte‐associated protein 4 and programmed cell death protein 1 (PD‐1)/programmed cell death ligand 1(PD‐L1) are the two most studied for HCC.…”

“…3 More recently, some new TKI drugs have been reported to be effective for advanced stage HCC in phase III studies: lenvatinib as the first line of therapy, and regorafenib as second-line therapy. 4,5 As a current research hotspot, blockade of cytotoxic T lymphocyte-associated protein 4 and programmed cell death protein 1 (PD-1)/ programmed cell death ligand 1(PD-L1) are the two most studied for HCC. Nivolumab, an anti-PD-1 antibody, received expedited FDA approval for the treatment of advanced HCC after failure or intolerance to sorafenib in 2017.…”