Combination Cancer Immunotherapy in Hepatocellular Carcinoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Kudo M
PROVIDER: S-EPMC5892358 | biostudies-literature | 2018 Mar
REPOSITORIES: biostudies-literature
Publications
Combination Cancer Immunotherapy in Hepatocellular Carcinoma.
Liver cancer 20180131 1
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Project description:Hepatocellular carcinoma (HCC) is the most frequent malignancy of the liver, which is considered the fourth leading cause of cancer-related death in the United States. Liver transplant and surgical resection are curative treatments for HCC, but only 10-15% of HCC patients are eligible candidates. The FDA-approved sorafenib is a multi-kinase inhibitor systemic therapy for advanced HCC that extends the overall survival by over 3 months when compared with placebo. Adoptive transfer of Natural Killer (NK) cells holds great promise for clinical cancer treatment. However, only limited clinical benefit has been achieved in cancer patients. Therefore, there is currently considerable interest in development of the combination of sorafenib and NK cells for the treatment of HCC patients. However, the mechanism of how sorafenib affects the function of NK cells remains to be comprehensively clarified. In this paper, we will discuss NK cell-based immunotherapies that are currently under preclinical and clinical investigation and its potential combination with sorafenib for improving the survival of HCC patients.
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Project description:For over a decade, sorafenib remained the only systemic agent with proven clinical efficacy for patients with advanced hepatocellular carcinoma (HCC). Recent years have seen a proliferation of agents. In the first line, lenvatinib was found to be non-inferior to sorafenib in terms of overall survival (OS), with significantly better progression-free survival and objective response rate. Meanwhile, encouraging efficacy signals were observed in phase I/II studies of immune checkpoint inhibitors as monotherapy in HCC. Although subsequent phase III trials failed to demonstrate statistically significant benefit in OS, other clinically meaningful outcomes were observed, including long-term disease control with a favorable toxicity profile. In addition, a synergistic response has been postulated based on the interplay between antiangiogenic molecular targeted agents and immunotherapy. On this basis, interest has turned toward combination strategies of immunotherapy with these standard-of-care medications in the hope of improving treatment efficacy for advanced HCC, while maintaining tolerable safety profiles. Indeed, preliminary results from phase I studies of lenvatinib plus pembrolizumab and atezolizumab plus bevacizumab have proved favorable, prompting phase III investigations in the frontline setting, and for atezolizumab plus bevacizumab, these positive findings have been substantiated by recent reporting of phase III data from IMbrave150. In this review, we will present the currently available data on combination therapy atezolizumab plus bevacizumab in advanced HCC, and compare these findings to other promising combination treatments, most notably that of lenvatinib plus pembrolizumab.
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