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Brief Report
July18, 2024
Claudia Angela MariaFulgenzi,MD1,2; BernhardScheiner,PhD1,3; AntonioD’Alessio,MD1,4; et al AmanMehan,MD1; Giulia F.Manfredi,MD1,4; CiroCelsa,PhD1,5; NaoshiNishida,MD6; CelinaAng,MD7; Thomas U.Marron,PhD7; LindaWu,MD7; AnwaarSaeed,MD8; BrookeWietharn,MD8; AntonellaCammarota,MD9,10; TizianaPressiani,MD10; MatthiasPinter,PhD3; RohiniSharma,PhD1; JaekyungCheon,MD11; Yi-HsiangHuang,PhD12,13,14; Pei-ChangLee,MD15,16; SamuelPhen,MD17; AnuhyaGampa,MD18; AnjanaPillai,PhD19; AndreaNapolitano,PhD20; CaterinaVivaldi,PhD21; FrancescaSalani,MD21,22; GianlucaMasi,PhD21; MariannaSilletta,PhD2; FedericaLo Prinzi,MD2; EmanuelaDi Giacomo,MD2; BrunoVincenzi,PhD2; DominikBettinger,PhD23; RobertThimme,PhD23; ArndtVogel,PhD24; MartinSchönlein,MD25; Johannvon Felden,MD26; KorneliusSchulze,PhD26; HenningWege,PhD26; Peter R.Galle,PhD27; MarioPirisi,PhD4; Joong-WonPark,PhD28; MasatoshiKudo,PhD6; LorenzaRimassa,MD9,10; Amit G.Singal,MD15,16; PaulEl Tomb,MD29; SusannaUlahannan,MD29; AlessandroParisi,MD30; Hong JaeChon,PhD11; Wei-FanHsu,PhD31; GiorgiaGhittoni,MD32; CalogeroCammà,PhD5; BenedettaStefanini,MD33; FrancoTrevisani,PhD33; Edoardo G.Giannini,PhD34,35; AlessioCortellini,PhD1,2; David JamesPinato,MD, PhD1,4
Author Affiliations Article Information
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1Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, England
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2Operative Research Unit of Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
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3Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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4Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
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5Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother and Child Care, Internal Medicine & Medical Specialties, University of Palermo, Palermo, Italy
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6Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
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7Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai Hospital, New York, New York
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8Department of Medicine, Division of Medical Oncology, Kansas University Cancer Center, Kansas City
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9Department of Biomedical Sciences, Humanitas University, Milan, Italy
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10Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
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11Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
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12Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan
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13Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan
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14Institute of Clinical Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
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15Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan
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16Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
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17Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas
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18Medical Oncology/TSET Phase 1 Program, Stephenson Cancer Center, Section of Gastroenterology, University of Oklahoma, Oklahoma City
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19Hepatology & Nutrition, the University of Chicago Medicine, Chicago, Illinois
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20The Royal Marsden National Health Service Foundation Trust, London, England
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21Unit of Medical Oncology 2, Azienda Ospedaliero- Universitaria Pisana, Pisa, Italy
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22Scuola Superiore Sant’Anna Pisa, Interdisciplinary Research Center, Pisa, Italy
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23Department of Gastroenterology, Hepatology, Endocrinology and Infectious Diseases, Freiburg University Medical Center, University of Freiburg, Freiburg, Germany
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24Hannover Medical School, Hannover, Germany
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25Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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26Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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27Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany
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28National Cancer Centre Hospital, Goyang, South Korea
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29Stephenson Cancer Center, Oklahoma City, Oklahoma
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30Department of Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria delle Marche, Ancona, Italy
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31Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
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32Gastroenterology Unit, Belcolle hospital, Viterbo, Italy
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33Semeiotics and Liver and Alcohol-Related Disease Unit, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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34Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
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35IRCCS Ospedale Policlinico San Martino, Genoa, Italy
JAMA Oncol. Published online July 18, 2024. doi:10.1001/jamaoncol.2024.2166
Full Text
Question Do patients with unresectable hepatocellular carcinoma (HCC) and suboptimal liver function benefit from immunotherapy vs best supportive care?
Findings In this case series of 343 patients with Child-Pugh class B liver dysfunction, immunotherapy-based systemic therapy was associated with significant reduction in the risk of death compared with best supportive care.
Meaning The results of this study suggest that immunotherapy may be a safe and effective option for patients with unresectable HCC and suboptimal liver function.
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.
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July 24, 2024
Immunotherapy vs Best Supportive Care for Patients With Hepatocellular Cancer With Child-Pugh B Dysfunction
fausto petrelli, MD | ASST BERGAMO OVEST
We are writing to present our comments on the study recently published by Fulgenzi et al. in JAMA Oncology titled "Immunotherapy vs Best Supportive Care for Patients With Hepatocellular Cancer With Child-Pugh B Dysfunction".1 This paper addresses a crucial issue in the management of patients with hepatocellular carcinoma (HCC) and moderate liver dysfunction (Child-Pugh B, CP-B). It provides compelling evidence for the efficacy of immune checkpoint inhibitors (ICIs) compared to best supportive care (BSC). The study, a retrospective, multicenter, international investigation, compares overall survival (OS) in patients receiving ICI-based therapies with those receiving BSC. The results demonstrate a significant survival benefit in the ICI group, with a median OS of 7.50 months compared to 4.04 months in the BSC group (HR, 0.59; 95% CI, 0.43-0.80; P < .001). These findings have profound implications. They challenge the conventional practice of reserving BSC for patients with CP-B liver dysfunction, suggesting that immunotherapy can provide significant benefits. Consequently, inclusive clinical trials targeting this high-risk population are warranted. Nevertheless, I believe it is important to consider additional aspects that warrant discussion: Selection Bias: Despite the use of propensity score weighting, there may still be unmeasured confounders that influence treatment allocation and outcomes. Generalizability: It would be valuable to understand the applicability of these findings in community settings where resource availability and patient management practices may differ. Safety Profile: The safety data emphasize the significance of careful patient selection and monitoring. Future prospective studies should further investigate the balance between efficacy and toxicity in this vulnerable patient population. Long-Term Outcomes: While the study provides important short-term survival data, long-term outcomes and measures of quality of life are essential for a comprehensive understanding of the impact of ICI therapy in CP-B patients. The study by Fulgenzi et al. establishes the foundation for future research and supports the inclusion of CP-B patients in clinical trials to validate these findings prospectively. The promising results advocate for a shift in the treatment paradigm for CP-B patients with HCC, who have traditionally only received supportive care. Thank you for providing the opportunity to discuss this significant work. I eagerly await further advancements in this critical area of oncology. Sincerely, Fausto Petrelli, MD References
Lorenzo Dottorini, MD
Oncology Unit, ASST Bergamo Ovest, Treviglio (BG) Italy
faupe@libero.it
1.Fulgenzi CAM, Scheiner B, D'Alessio A, et al. Immunotherapy vs Best Supportive Care for Patients With Hepatocellular Cancer With Child-Pugh B Dysfunction. JAMA Oncol. Published online July 18, 2024. doi:10.1001/jamaoncol.2024.2166
2.
CONFLICT OF INTEREST: None Reported
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Hepatobiliary Disease Gastroenterology and Hepatology Gastroenterology Gastrointestinal Cancer Hepatobiliary Cancer Oncology
Citation
Fulgenzi CAM, Scheiner B, D’Alessio A, et al. Immunotherapy vs Best Supportive Care for Patients With Hepatocellular Cancer With Child-Pugh B Dysfunction. JAMA Oncol. Published online July 18, 2024. doi:10.1001/jamaoncol.2024.2166
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