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

The oncologist

article

Ioannis A. Ziogas¹  Georgios Tsoulfas¹  Alexandros P. Evangeliou³  Dimitrios Giannis²  Muhammad H. Hayat⁵  Konstantinos S. Mylonas⁶  Samer Tohme⁷  David A. Geller⁷  Nahel Elias⁸  Lipika Goyal⁹ 

[1] First Department of Surgery, Aristotle University of Thessaloniki;Surgery Working Group, Society of Junior Doctors;Medicine Working Group, Society of Junior Doctors;Institute of Health Innovations and Outcomes Research, The Feinstein Institute for Medical Research;Department of Medicine, Division of Gastroenterology, Vanderbilt University Medical Center;Department of Cardiothoracic Surgery, Yale New Haven Hospital;Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, University of Pittsburgh Medical Center;Transplantation Unit, Department of Surgery, Massachusetts General Hospital and Harvard Medical School;Department of Medicine, Division of Medical Oncology, Massachusetts General Hospital and Harvard Medical School

关键词: Immune checkpoint inhibitors;    Immunotherapy;    Hepatocellular carcinoma;    PD-1 inhibitors;    CTLA-4 inhibitors;   

DOI  :  10.1002/onco.13638

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background Immune checkpoints inhibitors (ICIs) have emerged as a treatment option for several malignancies. Nivolumab, pembrolizumab, nivolumab plus ipilimumab, and atezolizumab plus bevacizumab have been approved for the management of advanced-stage hepatocellular carcinoma (HCC). We aimed to systematically review the literature and summarize the characteristics and outcomes of patients with HCC treated with ICIs. Methods A systematic literature search of PubMed, the Cochrane Library, and ClinicalTrials.gov was performed according to the PRISMA statement (end of search date: November 7, 2020). Quality of evidence assessment was also performed. Results Sixty-three articles including 2,402 patients were analyzed, 2,376 of whom received ICIs for unresectable HCC. Response to ICIs could be evaluated in 2,116 patients; the overall objective response rate (ORR) and disease control rate (DCR) were 22.7% and 60.7%, respectively, and the mean overall survival (OS) was 15.8 months. The ORR, DCR, and OS for nivolumab ( n = 846) were 19.7%, 51.1%, and 18.7 months, respectively; for pembrolizumab ( n = 435) they were 20.7%, 64.6% and 13.3 months, respectively. The combination of atezolizumab/bevacizumab ( n = 460) demonstrated an ORR and DCR of 30% and 77%, respectively. The overall rate of treatment discontinuation because of adverse events was 14.9%. Fifteen patients received ICIs in the liver transplant (LT) setting (one pre-LT for bridging, 14 for post-LT recurrence); fatal graft rejection was reported in 40.0% ( n = 6/15) and mortality in 80.0% ( n = 12/15). Conclusion ICIs are safe and effective against unresectable HCC, but caution is warranted regarding their use in the LT setting because of the high graft rejection rate. Implications for Practice This systematic review pooled the outcomes from studies reporting on the use of immune checkpoint inhibitors (ICIs) for the management of 2,402 patients with advanced-stage hepatocellular carcinoma (HCC), 2,376 of whom had unresectable HCC. The objective response rate and disease control rate were 22.7% and 60.7%, respectively, and the mean overall survival was 15.8 months. The overall rate of treatment discontinuation because of adverse events was 14.9%. Fifteen patients received ICIs in the liver transplant (LT) setting (one pre-LT for bridging, 14 for post-LT recurrence). Six of these patients experienced graft rejection (40.0%).

【 授权许可】

CC BY|CC BY-NC