The Role of Immunotherapy in Hepatocellular Carcinoma: A Systematic Review and Pooled Analysis of 2,402 Patients

Ziogas, Ioannis A.; Evangeliou, Alexandros; Giannis, Dimitrios; Hayat, Muhammad Hashim; Mylonas, Konstantinos S.; Tohme, Samer; Geller, David A.; Elias, Nahel; Goyal, Lipika; Tsoulfas, Georgios

doi:10.1002/onco.13638

Cited by 39 publications

(22 citation statements)

References 92 publications

(164 reference statements)

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“…However, among 15 patients who received CPI in the setting of liver transplant, fatal graft rejection was reported in 40% and the mortality rate was 80%. Thus, the authors warranted caution regarding use of CPI in this setting [ 118 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Trials of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Dyhl-Polk

Mikkelsen

Ladekarl

et al. 2021

JCM

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Introduction: Several immune checkpoint inhibitors (CPIs) are under clinical development in hepatocellular carcinoma (HCC) and the field is advancing rapidly. In this comprehensive review, we discuss published results and report on ongoing clinical trials. Methods: A literature search was carried out using PubMed and EMBASE; data reported at international meetings and clinicaltrials.gov were included as well. The search was updated 5 March 2021. We evaluated studies with monotherapy CPI’s, combinations of CPI’s and combinations of CPI’s with other treatment modalities separately. Only studies with at least 10 included patients were considered. Results: We identified 2649 records published in the English language literature. After review, 29 studies remained, including 12 studies with preliminary data only. The obtained overall response rate of PD-1/PDL-1 monotherapy in phase II studies in the second-line setting was 15–20% with disease control in approximately 60% of patients. The responses were of long duration in a subset of patients. Furthermore, the safety profiles were manageable. However, a phase III study comparing nivolumab with sorafenib in the first-line setting and a phase III study evaluating pembrolizumab versus best supportive care in the second-line setting did not meet their prespecified endpoints. More recently, a phase I/II study of nivolumab and ipilimumab has resulted in a response rate of approximately 30% with a median OS of 22 months in the second-line setting. Multiple trials have been initiated to evaluate CPIs in combination with molecularly targeted drugs, especially anti-angiogenic drugs or local therapy. A phase III study investigating atezolizumab plus bevacizumab versus sorafenib in the first-line setting showed significantly increased survival in the combination arm. Conclusions: The combination of atezolizumab and bevacizumab represents a new standard of care in the first-line setting for fit patients with preserved liver function. CPIs can produce durable tumor remission and induce long-standing anti-tumor immunity in a subgroup of patients with advanced HCC. Although phase III trials of CPI monotherapy have been negative, the combination of PD-1/PD-L1 inhibitors with other anti-angiogenic drugs, CTLA-4 inhibitors or other modalities may result in new treatment options for patients with HCC. Research on predictive biomarkers is crucial for further development of CPIs in HCC.

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Section: Discussionmentioning

confidence: 99%

Clinical Trials of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Dyhl-Polk

Mikkelsen

Ladekarl

et al. 2021

JCM

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“…The relationship between graft rejection and tumor response is still unclear because there is an insufficient number of cases or studies to evaluate. There are also limited predictive biomarkers to adapt immunotherapy for HCC patients in the setting of post LT [ 62 ]. On the other hand, the utility of immunotherapy as bridging therapy to LT has shown more acceptance in the transplant oncology community.…”

Section: Emerging Concepts In Transplant Oncologymentioning

confidence: 99%

Transplant Oncology: An Evolving Field in Cancer Care

Abdelrahim

Esmail

Abudayyeh

et al. 2021

Cancers

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Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The application of oncology, transplant medicine, and surgery to improve patients’ survival and quality of life is the core of transplant oncology. Hepatobiliary malignancies have been treated by liver transplantation (LT) with significant improved outcome. In addition, as the liver is the most common site of metastasis for colorectal cancer (CRC), patients with CRC who have stable unresectable liver metastases are good candidates for LT, and initial studies have shown improved survival compared to palliative systemic therapy. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years in a stepwise manner; however, they have only been shown to improve patient survival in the setting of limited systemic therapy options. This review illustrates the concept and history of transplant oncology as an evolving field for the management of hepatocellular carcinoma, intrahepatic biliary cancer, and liver-only metastasis of non-hepatobiliary carcinoma. The utility of immunotherapy in the transplant setting is discussed as well as the feasibility of using circulating tumor DNA for surveillance post-transplantation.

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“…More ICIs, such as tislelizumab, camrelizumab, durvalumab, and avelumab, are currently being evaluated in some ongoing clinical studies[ 18 , 41 , 42 ] (Table 1 ). ICIs were considered as a safe and effective method for advanced-stage HCC in a recent systematic review and pooled analysis of 2402 patients[ 43 ]. The results showed that the disease control rate, objective response rate, and mean OS rate were 60.7%, 22.7%, and 15.8 mo, respectively.…”

Section: Immunotherapymentioning

confidence: 99%

Thermal ablation and immunotherapy for hepatocellular carcinoma: Recent advances and future directions

Bo¹,

Sun²,

Yu³

et al. 2021

WJGO

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Hepatocellular carcinoma (HCC) is one of most common cancers that cause death in the world. Thermal ablation (TA) is an important alternative treatment method for HCC patients who are not appropriate for surgery or liver transplantation. Particularly for small and early HCCs, TA can be considered as the first-line curative treatment. However, local and distant recurrence rates are still high even though the TA equipment and technology develop rapidly. Immunotherapy is a novel systemic treatment method to enhance the anti-tumor immune response of HCC patients, which has the potential to reduce the tumor recurrence and metastasis. The combination of local TA and systemic immunotherapy for HCCs may be an ideal treatment for enhancing the efficacy of TA and controlling the recurrence. Herein we summarize the latest progress in TA, immunotherapy, and their combination for the treatment of patients with HCC and discuss the limitations and future research directions of the combined therapy.

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The Role of Immunotherapy in Hepatocellular Carcinoma: A Systematic Review and Pooled Analysis of 2,402 Patients

Cited by 39 publications

References 92 publications

Clinical Trials of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Clinical Trials of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Transplant Oncology: An Evolving Field in Cancer Care

Thermal ablation and immunotherapy for hepatocellular carcinoma: Recent advances and future directions

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