New Systemic Treatments in Advanced Hepatocellular Carcinoma

Abstract

The principal advancements in the treatment of hepatocellular carcinoma (HCC) are the use of new systemic treatments, such as lenvatinib in first‐line treatment and regorafenib, cabozantinib, and ramucirumab in second‐line treatment, because of their benefits in terms of overall survival. In addition, nivolumab as a second‐line agent was approved by the US Food and Drug Administration in 2017 based on improved radiological response data. Physicians and patients alike will greatly benefit from this expanded arsenal of treatments once all these new drugs for the treatment of HCC finally become available. Unfortunately, in our review of the available data, we found a conspicuous lack of approved systemic treatments for HCC in the distinct setting of after liver transplantation (LT). Careful evaluation of the clinical trials for approved systemic treatments of HCC is crucial when considering the best options for those with HCC recurrence after LT. Although several first‐line or second‐line treatments have been shown to be effective for HCC, each of these trials was composed of its own specific populations, and those with HCC recurrence after LT were excluded. We have also summarized from a critical and clinical point of view the issues involved in the management of patients who are candidates for systemic treatment in this era of multiple drugs for the same indication.

Preliminary experience on safety of regorafenib after sorafenib failure in recurrent hepatocellular carcinoma after liver transplantation

“…These data cover the gap of information on this special population, usually excluded from pivotal trials, and provide rational for using regorafenib after sorafenib in transplanted patients. 12,15,[24][25][26][27][28] In the past years, the safety profile and effectiveness of sorafenib in patients with recurrent HCC after liver transplantation has been confirmed by small cohort studies (ranging from 10 to 31 patients), performed in this population. 6,[8][9][10][11][12][13][14] These findings, but also the lack of alternative effective systemic treatment options, made sorafenib the standard of care in HCC recurrence after liver transplantation.…”

“…However, the available data are quite contradictory, generally coming from single-center experiences with only few patients enrolled. [6][7][8][9][10][11][12] Regorafenib is the first second-line systemic treatment that improved survival in patients with HCC who tolerated and progressed on sorafenib, as recently shown in the international, phase 3, randomized controlled trial RESORCE. 15 However, previous history of LT was an exclusion criterion in this study, as it was in all other phase III studies testing systemic therapies in advanced stage HCC.…”

“…15 However, previous history of LT was an exclusion criterion in this study, as it was in all other phase III studies testing systemic therapies in advanced stage HCC. 12,15 Thus, to date there are no data on safety and effectiveness of regorafenib as a second-line therapy in this particular setting. We conducted a multicenter retrospective study describing the safety and outcome of regorafenib in patients with recurrent HCC after LT who progressed on sorafenib treatment.…”

Long-term survival after resection of pharyngeal metastasis following living-donor liver transplantation for hepatocellular carcinoma: case report and review of literature

“…The efficacy of these drugs for treating recurrence after liver transplantation for HCC has been studied (42)(43)(44)(45); several reports indicated prolongation of survival, but there is no established therapeutic regimen and there is some concern regarding adverse effects on liver function. Clinical trials of chemotherapy for patients with HCC recurrence and/or postoperative adjuvant chemotherapy for patients at high risk of recurrence after liver transplantation are required (46). In addition, 2 years after pharyngeal polypectomy, recurrence of HCC was detected in the regional neck lymph nodes.…”

Secretory clusterin promotes hepatocellular carcinoma progression by facilitating cancer stem cell properties via AKT/GSK-3β/β-catenin axis

“…anti-angiogenic and MAP kinase inhibitor) has shown inhibitory effects on a broad spectrum of malignant phenotypes of HCC, including proliferation, angiogenesis, and metastasis [3]. However, low response rate and the high risk of resistance within 6 months limit the efficacy of sorafenib for HCC patients [4].…”