Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumab
Background & Aims: Atezolizumab/bevacizumab (A/B) is now a standard first-line treatment for advanced hepatocellular carcinoma (HCC), but the optimal second-line regimen is not known. We evaluated real-world treatment patterns and outcomes to investigate factors associated with post-progress...
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2025-02-01
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| author | Meng Wu Claudia A.M. Fulgenzi Antonio D’Alessio Alessio Cortellini Ciro Celsa Giulia F. Manfredi Bernardo Stefanini Y. Linda Wu Yi-Hsiang Huang Anwaar Saeed Angelo Pirozzi Tiziana Pressiani Lorenza Rimassa Martin Schoenlein Kornelius Schulze Johann von Felden Yehia Mohamed Ahmed O. Kaseb Arndt Vogel Natascha Roehlen Marianna Silletta Naoshi Nishida Masatoshi Kudo Caterina Vivaldi Lorenz Balcar Bernhard Scheiner Matthias Pinter Amit G. Singal Joshua Glover Susanna Ulahannan Fredrich Foerster Arndt Weinmann Peter R. Galle Neehar D. Parikh Wei-Fan Hsu Alessandro Parisi Hong Jae Chon David J. Pinato Celina Ang |
| author_facet | Meng Wu Claudia A.M. Fulgenzi Antonio D’Alessio Alessio Cortellini Ciro Celsa Giulia F. Manfredi Bernardo Stefanini Y. Linda Wu Yi-Hsiang Huang Anwaar Saeed Angelo Pirozzi Tiziana Pressiani Lorenza Rimassa Martin Schoenlein Kornelius Schulze Johann von Felden Yehia Mohamed Ahmed O. Kaseb Arndt Vogel Natascha Roehlen Marianna Silletta Naoshi Nishida Masatoshi Kudo Caterina Vivaldi Lorenz Balcar Bernhard Scheiner Matthias Pinter Amit G. Singal Joshua Glover Susanna Ulahannan Fredrich Foerster Arndt Weinmann Peter R. Galle Neehar D. Parikh Wei-Fan Hsu Alessandro Parisi Hong Jae Chon David J. Pinato Celina Ang |
| author_sort | Meng Wu |
| collection | DOAJ |
| description | Background & Aims: Atezolizumab/bevacizumab (A/B) is now a standard first-line treatment for advanced hepatocellular carcinoma (HCC), but the optimal second-line regimen is not known. We evaluated real-world treatment patterns and outcomes to investigate factors associated with post-progression survival (PPS). Methods: In this multicenter, international, retrospective study, we examined clinical characteristics and outcomes of patients with advanced HCC who progressed on first-line A/B. The primary outcome of PPS was defined as time from first radiographic progression on A/B to death. Results: A total of 406 patients alive after progression on first-line A/B were included in the final analysis, of whom 45.3% (n = 184) received best supportive treatment (BST) and 54.7% (n = 222) continued active systemic treatment. In the second line, 155 patients were treated with tyrosine kinase inhibitors (TKIs), 45 with immune checkpoint inhibitor (IO)-based regimens, and 3 had missing data. Median PPS of the whole cohort (mPPS) was 6.0 months (95% CI 5.2-7.2). On multivariate Cox regression analysis, absence of portal vein tumor thrombus, ECOG <2, and continued active treatment were predictors of better PPS. mPPS was significantly longer for patients who continued active treatment vs. BST (9.7 vs. 2.6 months; HR 0.41, p <0.001). In the second-line setting, patients treated with TKIs had a numerically shorter mPPS compared to those treated with IO (8.4 vs. 14.9 months; HR 1.37, p = 0.256). Conclusions: Continuation of active therapy after A/B progression was independently associated with better survival even after adjusting for baseline disease characteristics. mPPS with IO-based therapy exceeded a year, suggesting that IO continuation post-progression may retain benefit. The precise sequencing of TKI and IO regimens warrants further investigation. Impact and implications:: There is currently a lack of level 1 data on second-line treatment options for patients with advanced hepatocellular carcinoma who progress after frontline atezolizumab plus bevacizumab, as all second-line approvals were established during the frontline sorafenib era. Our study aims to fill in some of the knowledge gap by investigating real-world patient outcomes in the second-line treatment setting. Findings from this study show that patients who continued active treatment had improved post-progression survival compared to those who received best supportive care, and medication regimens incorporating tyrosine kinase inhibitors as well as immunotherapy agents were active. These results can help inform clinicians of possible treatment options for patients who progress after frontline atezolizumab plus bevacizumab while we await maturing data from randomized-controlled trials. |
| format | Article |
| id | doaj-art-32c4ec833716493d83190426ffbd64b3 |
| institution | Kabale University |
| issn | 2589-5559 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHEP Reports |
| spelling | doaj-art-32c4ec833716493d83190426ffbd64b32025-02-07T04:48:07ZengElsevierJHEP Reports2589-55592025-02-0172101232Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumabMeng Wu0Claudia A.M. Fulgenzi1Antonio D’Alessio2Alessio Cortellini3Ciro Celsa4Giulia F. Manfredi5Bernardo Stefanini6Y. Linda Wu7Yi-Hsiang Huang8Anwaar Saeed9Angelo Pirozzi10Tiziana Pressiani11Lorenza Rimassa12Martin Schoenlein13Kornelius Schulze14Johann von Felden15Yehia Mohamed16Ahmed O. Kaseb17Arndt Vogel18Natascha Roehlen19Marianna Silletta20Naoshi Nishida21Masatoshi Kudo22Caterina Vivaldi23Lorenz Balcar24Bernhard Scheiner25Matthias Pinter26Amit G. Singal27Joshua Glover28Susanna Ulahannan29Fredrich Foerster30Arndt Weinmann31Peter R. Galle32Neehar D. Parikh33Wei-Fan Hsu34Alessandro Parisi35Hong Jae Chon36David J. Pinato37Celina Ang38Division of Hematology/Oncology, Department of Medicine, Tisch Cancer Institute, Mount Sinai Hospital, New York, NY, USADivision of Cancer, Department of Surgery and Cancer, Imperial College London, London, United KingdomDivision of Cancer, Department of Surgery and Cancer, Imperial College London, London, United Kingdom; Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, ItalyDivision of Cancer, Department of Surgery and Cancer, Imperial College London, London, United Kingdom; Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyDivision of Cancer, Department of Surgery and Cancer, Imperial College London, London, United Kingdom; Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child-Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Palermo, ItalyDivision of Cancer, Department of Surgery and Cancer, Imperial College London, London, United Kingdom; Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, ItalyDivision of Cancer, Department of Surgery and Cancer, Imperial College London, London, United Kingdom; Department of Medical and Surgical Sciences, University of Bologna, Bologna, ItalyDivision of Hematology/Oncology, Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USAHealthcare and Service Center, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang Ming Chiao Tung University College of Medicine, Taipei, TaiwanDivision of Hematology/Oncology, Department of Medicine, University of Pittsburgh (UPMC), Pittsburgh, PA, USADepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, ItalyHumanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, ItalyDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, ItalyDepartment of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USAToronto General Hospital, Princess Margaret Cancer Centre, Toronto, ON, Canada; Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, GermanyDepartment of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Freiburg University Medical Center, Faculty of Medicine, Freiburg, Germany; Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Freiburg, GermanyOperative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, JapanDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, JapanDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy; Unit of Medical Oncology 2, University Hospital of Pisa, Pisa, ItalyDivision of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, AustriaDivision of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, AustriaDivision of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, AustriaDivision of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USAStephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAStephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USADepartment of Medicine, University Medical Centre Mainz, Mainz, GermanyDepartment of Medicine, University Medical Centre Mainz, Mainz, GermanyDepartment of Medicine, University Medical Centre Mainz, Mainz, GermanyDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USACenter for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, TaiwanDepartment of Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria delle Marche, Ancona, ItalyMedical Oncology, Department of Internal Medicine, CHA Bundang Medical Centre, CHA University, Seongnam, Republic of KoreaDivision of Cancer, Department of Surgery and Cancer, Imperial College London, London, United Kingdom; Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, ItalyDivision of Hematology/Oncology, Department of Medicine, Tisch Cancer Institute, Mount Sinai Hospital, New York, NY, USA; Corresponding author. Address: Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1079, New York, NY 10029, USA.Background & Aims: Atezolizumab/bevacizumab (A/B) is now a standard first-line treatment for advanced hepatocellular carcinoma (HCC), but the optimal second-line regimen is not known. We evaluated real-world treatment patterns and outcomes to investigate factors associated with post-progression survival (PPS). Methods: In this multicenter, international, retrospective study, we examined clinical characteristics and outcomes of patients with advanced HCC who progressed on first-line A/B. The primary outcome of PPS was defined as time from first radiographic progression on A/B to death. Results: A total of 406 patients alive after progression on first-line A/B were included in the final analysis, of whom 45.3% (n = 184) received best supportive treatment (BST) and 54.7% (n = 222) continued active systemic treatment. In the second line, 155 patients were treated with tyrosine kinase inhibitors (TKIs), 45 with immune checkpoint inhibitor (IO)-based regimens, and 3 had missing data. Median PPS of the whole cohort (mPPS) was 6.0 months (95% CI 5.2-7.2). On multivariate Cox regression analysis, absence of portal vein tumor thrombus, ECOG <2, and continued active treatment were predictors of better PPS. mPPS was significantly longer for patients who continued active treatment vs. BST (9.7 vs. 2.6 months; HR 0.41, p <0.001). In the second-line setting, patients treated with TKIs had a numerically shorter mPPS compared to those treated with IO (8.4 vs. 14.9 months; HR 1.37, p = 0.256). Conclusions: Continuation of active therapy after A/B progression was independently associated with better survival even after adjusting for baseline disease characteristics. mPPS with IO-based therapy exceeded a year, suggesting that IO continuation post-progression may retain benefit. The precise sequencing of TKI and IO regimens warrants further investigation. Impact and implications:: There is currently a lack of level 1 data on second-line treatment options for patients with advanced hepatocellular carcinoma who progress after frontline atezolizumab plus bevacizumab, as all second-line approvals were established during the frontline sorafenib era. Our study aims to fill in some of the knowledge gap by investigating real-world patient outcomes in the second-line treatment setting. Findings from this study show that patients who continued active treatment had improved post-progression survival compared to those who received best supportive care, and medication regimens incorporating tyrosine kinase inhibitors as well as immunotherapy agents were active. These results can help inform clinicians of possible treatment options for patients who progress after frontline atezolizumab plus bevacizumab while we await maturing data from randomized-controlled trials.http://www.sciencedirect.com/science/article/pii/S2589555924002362Hepatocellular carcinomaatezolizumabbevacizumabsecond-line therapyimmune checkpoint inhibitorsimmunotherapy |
| spellingShingle | Meng Wu Claudia A.M. Fulgenzi Antonio D’Alessio Alessio Cortellini Ciro Celsa Giulia F. Manfredi Bernardo Stefanini Y. Linda Wu Yi-Hsiang Huang Anwaar Saeed Angelo Pirozzi Tiziana Pressiani Lorenza Rimassa Martin Schoenlein Kornelius Schulze Johann von Felden Yehia Mohamed Ahmed O. Kaseb Arndt Vogel Natascha Roehlen Marianna Silletta Naoshi Nishida Masatoshi Kudo Caterina Vivaldi Lorenz Balcar Bernhard Scheiner Matthias Pinter Amit G. Singal Joshua Glover Susanna Ulahannan Fredrich Foerster Arndt Weinmann Peter R. Galle Neehar D. Parikh Wei-Fan Hsu Alessandro Parisi Hong Jae Chon David J. Pinato Celina Ang Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumab JHEP Reports Hepatocellular carcinoma atezolizumab bevacizumab second-line therapy immune checkpoint inhibitors immunotherapy |
| title | Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumab |
| title_full | Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumab |
| title_fullStr | Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumab |
| title_full_unstemmed | Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumab |
| title_short | Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumab |
| title_sort | second line treatment patterns and outcomes in advanced hcc after progression on atezolizumab bevacizumab |
| topic | Hepatocellular carcinoma atezolizumab bevacizumab second-line therapy immune checkpoint inhibitors immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2589555924002362 |
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