Author information

• ¹Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, England.
• ²Operative Research Unit of Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.
• ³Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
• ⁴Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.
• ⁵Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother and Child Care, Internal Medicine & Medical Specialties, University of Palermo, Palermo, Italy.
• ⁶Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
• ⁷Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai Hospital, New York, New York.
• ⁸Department of Medicine, Division of Medical Oncology, Kansas University Cancer Center, Kansas City.
• ⁹Department of Biomedical Sciences, Humanitas University, Milan, Italy.
• ¹⁰Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
• ¹¹Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
• ¹²Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan.
• ¹³Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan.
• ¹⁴Institute of Clinical Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
• ¹⁵Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
• ¹⁶Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
• ¹⁷Medical Oncology/TSET Phase 1 Program, Stephenson Cancer Center, Section of Gastroenterology, University of Oklahoma, Oklahoma City.
• ¹⁸Hepatology & Nutrition, the University of Chicago Medicine, Chicago, Illinois.
• ¹⁹The Royal Marsden National Health Service Foundation Trust, London, England.
• ²⁰Unit of Medical Oncology 2, Azienda Ospedaliero- Universitaria Pisana, Pisa, Italy.
• ²¹Scuola Superiore Sant'Anna Pisa, Interdisciplinary Research Center, Pisa, Italy.
• ²²Department of Gastroenterology, Hepatology, Endocrinology and Infectious Diseases, Freiburg University Medical Center, University of Freiburg, Freiburg, Germany.
• ²³Hannover Medical School, Hannover, Germany.
• ²⁴Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
• ²⁵Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
• ²⁶Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany.
• ²⁷National Cancer Centre Hospital, Goyang, South Korea.
• ²⁸Stephenson Cancer Center, Oklahoma City, Oklahoma.
• ²⁹Department of Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria delle Marche, Ancona, Italy.
• ³⁰Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
• ³¹Gastroenterology Unit, Belcolle hospital, Viterbo, Italy.
• ³²Semeiotics and Liver and Alcohol-Related Disease Unit, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
• ³³Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy.
• ³⁴IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Abstract

Importance: Whether patients with Child-Pugh class B (CP-B) cancer with unresectable hepatocellular carcinoma (uHCC) benefit from active anticancer treatment vs best supportive care (BSC) is debated.

Objective: To evaluate the association of immune checkpoint inhibitor (ICI)-based therapies vs BSC with overall survival (OS) of patients with uHCC and CP-B liver dysfunction.

Design, setting, and participants: This retrospective, multicenter, international clinical case series examined data of patients with CP-B with uHCC who were receiving first-line ICI-based regimens from September 2017 to December 2022 whose data were extracted from an international consortium and compared with a cohort of patients with CP-B receiving BSC. Patients were treated in tertiary care centers across Europe, US, and Asia in routine clinical practice. After applying the inclusion criteria, 187 and 156 patients were left in the ICI and BSC groups, respectively. The propensity score was calculated for the following variables: age, alpha-fetoprotein levels, Child-Pugh score, extrahepatic spread, portal vein tumor thrombosis, cirrhosis, ascites, and baseline Eastern Cooperative Oncology Group performance status.

Exposures: Patients in the ICI group received first-line systemic therapy with either atezolizumab plus bevacizumab (A+B) (n = 141) or nivolumab (n = 46).

Main outcomes and measures: OS in the inverse probability of treatment weighting (IPTW) populations was the main outcome, and it was estimated with Kaplan-Meier method; univariable Cox regression test was used to make comparisons between the 2 groups.

Results: The median age was 66 (IQR, 61-72) and 73 (IQR, 66-81) years in the ICI (33 women [18%]) and BSC groups (41 women [26%]), respectively. In the IPTW populations, median OS was significantly longer in the ICI group (7.50 months; 95% CI, 5.62-11.15) compared with BSC (4.04 months; 95% CI, 3.03-5.03; hazard ratio, 0.59; 95% CI, 0.43-0.80; P < .001). Multivariable analysis confirmed that ICI exposure was associated with a reduction of approximately 50% in the risk of death (hazard ratio, 0.55; 95% CI, 0.35-0.86; P < .001), and the presence of portal vein tumor thrombosis, an Eastern Cooperative Oncology Group performance score of greater than 1, and alpha-fetoprotein levels of 400 ng/mL or greater were associated with increased risk of death.

Conclusions and relevance: The results of this case series provide comparative evidence of improved survival in association with ICI treatment compared with BSC in patients with uHCC with CP-B liver dysfunction.