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Hepatobiliary cancers and immunotherapy: where are we now and where are we heading?

ABSTRACT: Primary liver cancers are a heterogenous collection of diseases with variable natural histories and treatments. This review article will focus on hepatocellular carcinoma (HCC), intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer, and the use of immune checkpoint inhibitors (ICIs) in their treatment. This will include the currently studied, approved uses as well as the potential future roles of ICIs in the treatment of cancers of the hepatobiliary system through recent updates on ongoing studies and discussion of phase III studies underway. Currently, only two ICIs are approved for use in hepatobiliary cancers: nivolumab and pembrolizumab. First, pembrolizumab was approved for either microsatellite instability-high (MSI-H) or DNA mismatch repair deficient (dMMR) unresectable, or metastatic solid tumors, including HCC and biliary tract cancer (BTC) in May 2017. After CheckMate-040, nivolumab gained approval in late 2017 in the second-line setting for patients with advanced HCC and Child-Pugh A or B7 liver disease. Pembrolizumab was granted FDA approval in 2018 in the second-line setting after publication of KEYNOTE-224 for patients with advanced HCC and Child-Pugh A liver disease. All three approvals were independent of PD-L1 tumor or immune cell expression. Several other ICIs have been studied in various aspects of these diverse diseases including resectable disease and the advanced, unresectable, or metastatic setting from first-line to later line after failed systemic therapies. Some of these agents are also being assessed in combination with currently utilized tyrosine kinase inhibitors (TKIs) and/or chemotherapy. Lastly, we draw attention to phase III clinical trials in ICIs that are currently recruiting and will be approaching completion in the next 5 years, potentially altering the landscape of treatment in hepatobiliary malignancies for generations to come.

SUBMITTER: Zayac A

PROVIDER: S-EPMC7061229 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Hepatobiliary cancers and immunotherapy: where are we now and where are we heading?

Zayac Adam A Almhanna Khaldoun K

Translational gastroenterology and hepatology 20200105

Primary liver cancers are a heterogenous collection of diseases with variable natural histories and treatments. This review article will focus on hepatocellular carcinoma (HCC), intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer, and the use of immune checkpoint inhibitors (ICIs) in their treatment. This will include the currently studied, approved uses as well as the potential future roles of ICIs in the treatment of cancers of the hepatobiliary system through recent updat ...[more]

PMID: 32190776

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Project description:Immunotherapy has demonstrated its effectiveness in many cancers. In hepatocellular carcinoma (HCC), promising results shown in the first phase II studies evaluating anti-PD-1 or anti-PD-L1 monotherapies resulted in their approval in the United States. Approval was not obtained in Europe; subsequent randomized studies in first- or second-line treatment did not confirm these initial results. However, first data with immunotherapy plus antiangiogenic treatments or dual immunotherapy combinations were positive. In this context, the combination of bevacizumab and atezolizumab took the lead. The IMbrave150 trial revealed an improved objective response rate (ORR), progression-free survival, and overall survival with this combination versus the previous standard, sorafenib. Subsequent results of dual immunotherapy with the anti-CTLA-4 and anti-PD-1 monotherapies tremelimumab and durvalumab (also superior to sorafenib monotherapy) confirmed the value of using a combination in first-line treatment. These significant therapeutic advances, and the increase in ORR, raise two main questions. Whereas response was very limited with previous treatments, the ORR reported with these new combinations are between 20% and 30%. This raises the question of whether immunotherapy (ICI single agent, combination of ICI with antiangiogenic agent or other antitumoral treatment) can be used in patients beyond those in BCLC group C, the traditional candidate group for systemic therapy. We have thus seen an increasing number of patients previously treated with trans-arterial chemoembolization (BCLC group B) receiving these new treatments, and we develop the results of several studies combining loco-regional therapies and immunotherapy-based systemic treatments. The other major question is that of how and when to use these medical treatments as "adjuvants" to interventional radiology or surgery; the results of several works are discussed for this purpose. In this review, we cover all of these points in a fairly comprehensive manner.

Dataset Information

Hepatobiliary cancers and immunotherapy: where are we now and where are we heading?

Publications

Hepatobiliary cancers and immunotherapy: where are we now and where are we heading?

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