Immunotherapies for hepatocellular carcinoma

Abstract

Cases of hepatocellular carcinoma (HCC) are rapidly rising. This is particularly the case in the Western world, as a result of increasing rates of chronic liver disease, secondary to lifestyle‐associated risk factors and the lack of an established screening programme for the general population. Traditionally, radical/curative treatment options for HCC, including liver transplantation and surgical resection are reserved for the minority of patients, presenting with an early stage cancer. For patients with advanced disease, Sorafenib and Lenvatinib were, until recently, the only licensed systemic treatments, and provided only limited survival benefits at the cost of a multitude of potential side effects. Recent scientific advances in the field of cancer immunotherapy have renewed significant interest in advanced HCC, in order to fulfil this apparent area of unmet clinical need. This has led to the success and recent regulatory approval of an Atezolizumab/Bevacizumab combination for the first‐line treatment of advanced HCC following results from the IMbrave150 clinical trial in 2019, with further immune checkpoint inhibitors currently undergoing testing in advanced clinical trials. Furthermore, other cancer immunotherapies, including chimeric antigen receptor T‐cells, dendritic cell vaccines and oncolytic viruses are also in early stage clinical trials, for the treatment of advanced HCC. This review will summarise the major approaches that have been and are currently in development for the systemic treatment of advanced HCC, their advantages, drawbacks, and predictions of where this revolutionary treatment field will continue to travel for the foreseeable future.

Feasibility and Tolerability of Lenvatinib, Plus PD-1 Blockades for Patients with Unresectable Hepatocellular Carcinoma: A Retrospective Exploratory Study

“… 9 Among these regimens, lenvatinib seemed to be the most commonly used regimen for the patients in clinical practice. Unfortunately, similar to the clinical activity of PD-1 inhibitors monotherapy clinically (ORR <20%), 10 the ORR of lenvatinib monotherapy was also disappointing clinically (ORR <30%), 22 which highlighted the necessity to investigate new combination regimens to expand the potential patients who might benefit from lenvatinib-based administration.…”

“…In view of the physiological role of liver in processing extraneous drugs and the first-pass metabolism, HCC might naturally exhibit a relatively immunosuppressed state that was heavily regulated by the immune system, which suggested that immunotherapy (PD-1 blockades) might play a pivotal role to reverse the process in the tumor and help T cells to kill the tumor cells. 10 Consequently, the potential significance of PD-1 blockades in HCC had been proved by pembrolizumab, nivolumab, and camrelizumab as second-line treatment in China based on the results of Phase II clinical trials. 11 Unfortunately, the ORR of the PD-1 blockades monotherapy among patients with HCC ranged from 15–20% and all the PD-1 blockades failed to improve OS ultimately, which highlighted that immune checkpoint inhibitor-based regimens might be of potential significance for patients with unresectable HCC clinically.…”

Terapias sistémicas en carcinoma hepatocelular: secuencia de tratamientos

“…La inmunoterapia ha cambiado el panorama del tratamiento de pacientes con tumores sólidos recurrentes y con metástasis, tales como melanoma maligno y cáncer de pulmón de células no pequeñas [27,28]. La aplicación de los regímenes de inmunoterapia en CHC, con resultados excelentes en términos de seguridad y eficacia, ha revolucionado el tratamiento de estos pacientes.…”

Novel Gene Signatures as Prognostic Biomarkers for Predicting the Recurrence of Hepatocellular Carcinoma

“…Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the third leading cause of cancer-related mortality worldwide [ 1 ]. Immunotherapy is a systemic treatment option, with immune checkpoint inhibitors such as tyrosine kinase inhibitors (e.g., lenvatinib, cabozantinib, regorafenib) and anti-angiogenic monoclonal antibodies (ramucirumab) [ 2 , 3 , 4 ]; however, the response to ICIs is only 20–30% of patients [ 5 ]. Surgical resection is a curative treatment option which is currently chosen first for HCC [ 6 ]; however, up to 70% of patients who undergo surgical resection may experience recurrence of HCC, which can affect their long-term prognosis [ 7 ].…”