Neoadjuvant atezolizumab plus bevacizumab prior liver transplantation for hepatocellular carcinoma
Background & Aims: The combination of atezolizumab and bevacizumab offers a novel approach to immunomodulation, showing efficacy as a primary treatment in advanced hepatocellular carcinoma (HCC). Concerns about graft safety and rejection have limited its exploration in the neoadjuvant settin...
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Elsevier
2025-02-01
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| Series: | JHEP Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555924002507 |
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| author | Parissa Tabrizian Rebecca Marino Sherrie Bhoori Marcus Zeitlhoefler Neil Mehta Vanessa Banz Salvatore Gruttadauria Massimo Iavarone Chiara Mazzarelli Nicolò Simonotti Francis Yao Vincenzo Mazzaferro Josep M. Llovet |
| author_facet | Parissa Tabrizian Rebecca Marino Sherrie Bhoori Marcus Zeitlhoefler Neil Mehta Vanessa Banz Salvatore Gruttadauria Massimo Iavarone Chiara Mazzarelli Nicolò Simonotti Francis Yao Vincenzo Mazzaferro Josep M. Llovet |
| author_sort | Parissa Tabrizian |
| collection | DOAJ |
| description | Background & Aims: The combination of atezolizumab and bevacizumab offers a novel approach to immunomodulation, showing efficacy as a primary treatment in advanced hepatocellular carcinoma (HCC). Concerns about graft safety and rejection have limited its exploration in the neoadjuvant setting of liver transplantation (LT). In this study, we investigate the clinical efficacy and the safety profile of pre-transplant administration of atezolizumab and bevacizumab for HCC. Methods: Herein, we performed a prospective assessment of 17 patients with HCC treated with neoadjuvant preoperative atezolizumab and bevacizumab prior to LT for HCC, obtained from December 2020 and December 2023 at seven Western transplant centers. Results: Among the 17 patients with HCC included in the study, 16 (94.1%) had a tumor burden outside of Milan criteria. Neoadjuvant locoregional therapies along with the administration of atezolizumab plus bevacizumab (median: 5 months; discontinued at least 4 weeks prior to LT) led to an objective response rate of 94% (complete response: 59%), downstaging to within Milan criteria (82%) and a pathological response at explant examination of 88%. Grade 3-4 treatment-related adverse events accounted for 17.6% of cases and were manageable. During the 25-month median follow-up period, two cases of mild (rejection activity index ≤4), biopsy-proven rejection were reported but no instances of severe allograft rejection or graft loss were reported. The 1-year and 3-year post-LT survival rates were 94.2% and 88.2%, respectively. Conclusions: This study highlights the favorable oncological and survival outcomes associated with atezolizumab and bevacizumab treatment in the pre-LT setting. This immune-based combination was safe in terms of treatment-related adverse events, and absence of severe post-transplant rejection or graft loss. These preliminary results could pave the way for expanding transplant eligibility criteria in patients at more advanced HCC stages. Impact and Implications:: Studies on the combination of atezolizumab and bevacizumab in the neoadjuvant setting prior to liver transplantation for hepatocellular carcinoma have been limited, despite its potential to enhance anti-tumor responses and downstaging, owing to concerns about its safety profile. Among 17 patients who underwent successful liver transplantation following neoadjuvant atezolizumab/bevacizumab, 82% achieved downstaging to within Milan criteria, 94% radiological objective response and 88% pathology response, without drop-outs due to treatment-related adverse events or graft loss. The neoadjuvant combination of atezolizumab plus bevacizumab prior to liver transplantation for hepatocellular carcinoma shows an encouraging safety profile and stands out as a promising pre-transplant optimization treatment, leading to improved oncological outcomes. |
| format | Article |
| id | doaj-art-57142fa22e3e4342a57c2d8163db6836 |
| institution | Kabale University |
| issn | 2589-5559 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
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| series | JHEP Reports |
| spelling | doaj-art-57142fa22e3e4342a57c2d8163db68362025-02-07T04:48:07ZengElsevierJHEP Reports2589-55592025-02-0172101246Neoadjuvant atezolizumab plus bevacizumab prior liver transplantation for hepatocellular carcinomaParissa Tabrizian0Rebecca Marino1Sherrie Bhoori2Marcus Zeitlhoefler3Neil Mehta4Vanessa Banz5Salvatore Gruttadauria6Massimo Iavarone7Chiara Mazzarelli8Nicolò Simonotti9Francis Yao10Vincenzo Mazzaferro11Josep M. Llovet12Mount Sinai Liver Cancer Program, RMTI and Divisions of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Corresponding author. Address: Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy, New York, NY, 10029, USA.Mount Sinai Liver Cancer Program, RMTI and Divisions of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USADivision of HPB Surgery, Hepatology and Liver Transplantation, University of Milan and Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyMount Sinai Liver Cancer Program, RMTI and Divisions of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USADivision of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco CA, USADepartment of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, SwitzerlandDepartment Abdominal Center UPMC (University of Pittsburgh Medical Center), Palermo, and Department of Surgery and Medical and Surgical Specialties, University of Catania, ItalyDivision of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, CRC ''A. M. and A. Migliavacca'' Centre for Liver Disease, University of Milan, Milan, ItalyHepatology and Gastroenterology, ASST GOM Niguarda, Milan, ItalyDivision of HPB Surgery, Hepatology and Liver Transplantation, University of Milan and Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyDivision of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco CA, USADivision of HPB Surgery, Hepatology and Liver Transplantation, University of Milan and Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyMount Sinai Liver Cancer Program, RMTI and Divisions of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Liver Cancer Translational Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats, Barcelona, SpainBackground & Aims: The combination of atezolizumab and bevacizumab offers a novel approach to immunomodulation, showing efficacy as a primary treatment in advanced hepatocellular carcinoma (HCC). Concerns about graft safety and rejection have limited its exploration in the neoadjuvant setting of liver transplantation (LT). In this study, we investigate the clinical efficacy and the safety profile of pre-transplant administration of atezolizumab and bevacizumab for HCC. Methods: Herein, we performed a prospective assessment of 17 patients with HCC treated with neoadjuvant preoperative atezolizumab and bevacizumab prior to LT for HCC, obtained from December 2020 and December 2023 at seven Western transplant centers. Results: Among the 17 patients with HCC included in the study, 16 (94.1%) had a tumor burden outside of Milan criteria. Neoadjuvant locoregional therapies along with the administration of atezolizumab plus bevacizumab (median: 5 months; discontinued at least 4 weeks prior to LT) led to an objective response rate of 94% (complete response: 59%), downstaging to within Milan criteria (82%) and a pathological response at explant examination of 88%. Grade 3-4 treatment-related adverse events accounted for 17.6% of cases and were manageable. During the 25-month median follow-up period, two cases of mild (rejection activity index ≤4), biopsy-proven rejection were reported but no instances of severe allograft rejection or graft loss were reported. The 1-year and 3-year post-LT survival rates were 94.2% and 88.2%, respectively. Conclusions: This study highlights the favorable oncological and survival outcomes associated with atezolizumab and bevacizumab treatment in the pre-LT setting. This immune-based combination was safe in terms of treatment-related adverse events, and absence of severe post-transplant rejection or graft loss. These preliminary results could pave the way for expanding transplant eligibility criteria in patients at more advanced HCC stages. Impact and Implications:: Studies on the combination of atezolizumab and bevacizumab in the neoadjuvant setting prior to liver transplantation for hepatocellular carcinoma have been limited, despite its potential to enhance anti-tumor responses and downstaging, owing to concerns about its safety profile. Among 17 patients who underwent successful liver transplantation following neoadjuvant atezolizumab/bevacizumab, 82% achieved downstaging to within Milan criteria, 94% radiological objective response and 88% pathology response, without drop-outs due to treatment-related adverse events or graft loss. The neoadjuvant combination of atezolizumab plus bevacizumab prior to liver transplantation for hepatocellular carcinoma shows an encouraging safety profile and stands out as a promising pre-transplant optimization treatment, leading to improved oncological outcomes.http://www.sciencedirect.com/science/article/pii/S2589555924002507hepatocellular carcinomaliver transplantationimmunotherapyatezolizumabbevacizumabImmune Checkpoint Inhibitors |
| spellingShingle | Parissa Tabrizian Rebecca Marino Sherrie Bhoori Marcus Zeitlhoefler Neil Mehta Vanessa Banz Salvatore Gruttadauria Massimo Iavarone Chiara Mazzarelli Nicolò Simonotti Francis Yao Vincenzo Mazzaferro Josep M. Llovet Neoadjuvant atezolizumab plus bevacizumab prior liver transplantation for hepatocellular carcinoma JHEP Reports hepatocellular carcinoma liver transplantation immunotherapy atezolizumab bevacizumab Immune Checkpoint Inhibitors |
| title | Neoadjuvant atezolizumab plus bevacizumab prior liver transplantation for hepatocellular carcinoma |
| title_full | Neoadjuvant atezolizumab plus bevacizumab prior liver transplantation for hepatocellular carcinoma |
| title_fullStr | Neoadjuvant atezolizumab plus bevacizumab prior liver transplantation for hepatocellular carcinoma |
| title_full_unstemmed | Neoadjuvant atezolizumab plus bevacizumab prior liver transplantation for hepatocellular carcinoma |
| title_short | Neoadjuvant atezolizumab plus bevacizumab prior liver transplantation for hepatocellular carcinoma |
| title_sort | neoadjuvant atezolizumab plus bevacizumab prior liver transplantation for hepatocellular carcinoma |
| topic | hepatocellular carcinoma liver transplantation immunotherapy atezolizumab bevacizumab Immune Checkpoint Inhibitors |
| url | http://www.sciencedirect.com/science/article/pii/S2589555924002507 |
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