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Comparative Study
. 2024 Sep 1;10(9):1253-1258.
doi: 10.1001/jamaoncol.2024.2166.

Immunotherapy vs Best Supportive Care for Patients With Hepatocellular Cancer With Child-Pugh B Dysfunction

Claudia Angela Maria Fulgenzi  1   2 , Bernhard Scheiner  1   3 , Antonio D'Alessio  1   4 , Aman Mehan  1 , Giulia F Manfredi  1   4 , Ciro Celsa  1   5 , Naoshi Nishida  6 , Celina Ang  7 , Thomas U Marron  7 , Linda Wu  7 , Anwaar Saeed  8 , Brooke Wietharn  8 , Antonella Cammarota  9   10 , Tiziana Pressiani  10 , Matthias Pinter  3 , Rohini Sharma  1 , Jaekyung Cheon  11 , Yi-Hsiang Huang  12   13   14 , Pei-Chang Lee  13   15 , Samuel Phen  16 , Anuhya Gampa  17 , Anjana Pillai  18 , Andrea Napolitano  19 , Caterina Vivaldi  20 , Francesca Salani  20   21 , Gianluca Masi  20 , Marianna Silletta  2 , Federica Lo Prinzi  2 , Emanuela Di Giacomo  2 , Bruno Vincenzi  2 , Dominik Bettinger  22 , Robert Thimme  22 , Arndt Vogel  23 , Martin Schönlein  24 , Johann von Felden  25 , Kornelius Schulze  25 , Henning Wege  25 , Peter R Galle  26 , Mario Pirisi  4 , Joong-Won Park  27 , Masatoshi Kudo  6 , Lorenza Rimassa  9   10 , Amit G Singal  13   15 , Paul El Tomb  28 , Susanna Ulahannan  28 , Alessandro Parisi  29 , Hong Jae Chon  11 , Wei-Fan Hsu  30 , Giorgia Ghittoni  31 , Calogero Cammà  5 , Benedetta Stefanini  32 , Franco Trevisani  32 , Edoardo G Giannini  33   34 , Alessio Cortellini  1   2 , David James Pinato  1   4
Affiliations
Comparative Study

Immunotherapy vs Best Supportive Care for Patients With Hepatocellular Cancer With Child-Pugh B Dysfunction

Claudia Angela Maria Fulgenzi et al. JAMA Oncol. .

Erratum in

  • Error in Figure 1.
    [No authors listed] [No authors listed] JAMA Oncol. 2024 Sep 1;10(9):1294. doi: 10.1001/jamaoncol.2024.3947. JAMA Oncol. 2024. PMID: 39297926 Free PMC article. No abstract available.

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Scheiner reported personal fees from AbbVie, Ipsen, Gilead, Eisai, and Roche and grants from AstraZeneca and Eisai outside the submitted work. Dr D’Alessio reported personal fees from Roche, AstraZeneca, and Chugai outside the submitted work. Dr Celsa reported personal fees from Eisai, MSD, AstraZeneca, and Roche outside the submitted work. Dr Marron reported service on advisory and/or data safety monitoring boards for Rockefeller University, Regeneron, AbbVie, Merck, Bristol-Meyers Squibb, Boehringer Ingelheim, Atara, AstraZeneca, Genentech, Celldex, Chimeric, DrenBio, Glenmark, Simcere, Surface, G1 Therapeutics, NGMbio, DBV Technologies, Arcus, Fate, Ono, Larkspur, and Astellas and grants from the National Institutes of Health (National Cancer Institute), the Cancer Research Institute, Regeneron, Genentech, Bristol-Myers Squibb, Merck, and Boehringer Ingelheim. Dr Saeed reported personal fees from AstraZeneca, Bristol-Myers Squibb, Merck, Exelixis, Pfizer, Xilio Therapeutics, Taiho, Amgen, Autem Therapeutics, KAHR Medical, Arcus Therapeutics, and Daiichi Sankyo and grants from AstraZeneca, Bristol-Myers Squibb, Merck, Clovis, Exelixis, Actuate therapeutics, Incyte Corporation, Daiichi Sankyo, Five Prime Therapeutics, Amgen, Innovent biologics, Dragonfly Therapeutics, Oxford Biotherapeutics, Arcus Therapeutics, and KAHR Medical outside the submitted work. Dr Pressiani reported personal fees from Bayer, Ipsen and Astra Zeneca and research support from Roche Bayer, and AstraZeneca during the conduct of the study. Dr Cheon reported grants from Bayer. Dr Huang reported grants from Gilead, AstraZeneca, and BMS and nonfinancial support from Eisai and MSD outside the submitted work. Dr Pillai reported personal fees from Eisai, Genentech, Exelixis, AstraZeneca, and Replimune outside the submitted work. Dr Vivaldi reported personal fees from Roche, AstraZeneca, MSD, Taiho Oncology, Servier, and BMS; nonfinancial support from Roche, AstraZeneca, and MSD; and speaking fees from Terumo outside the submitted work. Dr Bettinger reported personal fees from Gore and Falk Foundation and grants from Gilead outside the submitted work. Dr Vogel reported personal fees from Roche, MSD, BMS, AstraZeneca,Eisai, Terumo, and Beigene outside the submitted work. Dr Wege reported personal fees from Roche, AstraZeneca, and Eisai outside the submitted work. Dr Galle reported personal fees from Roche, BMS, MSD, AstraZeneca, Eisai, Ipsen, Guerbet, Boston Scientific, and Lilly and grants from Bayer outside the submitted work. Dr Park reported grants from Ono-BMS, Roche, AstraZeneca, and MSD during the conduct of the study as well as personal fees from Roche, AstraZeneca, Bigene, and Eisai outside the submitted work. Dr Kudo reported personal fees from Eisai and Chugai outside the submitted work. Dr Rimassa reported personal fees from AstraZeneca, Basilea, Bayer, BMS, Eisai, Elevar Therapeutics, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Jazz Pharmaceuticals, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, and Zymeworkss outside the submitted work. Dr Singal reported personal fees from Genentech/Roche, AstraZeneca, Eisai, Bayer, Exelixis, Boston Scientific, Sirtex, FujiFilm Medical Sciences, Exact Sciences, Glycotest, Universal Dx, Freenome, GRAIL, and HistoSonics outside the submitted work. Dr Ulahannan reported grants from AbbVie, Adlai Nortye, ArQule, Astra Zeneca, Atreca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene Corporation, Ciclomed LLC, Erasca, Evelo Biosciences, Exelexis, G1 Therapeutics, GlaxoSmithKline GSK, IGM Biosciences, Incyte, Isofol, Klus Pharma, Macrogenics, Merck, Mersana Therapeutics, OncoMed Pharmaceuticals, Pfizer, Regeneron Pharmaceuticals, Revolution Medicines, Synermore Biologics Co, Takeda, Tarveda Therapeutics, Tesaro, Tempest Therapeutics, and Vigeo Therapeutics Inc during the conduct of the study as well as grants from AbbVie, Adlai Nortye, ArQule, AstraZeneca, Atreca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene Corporation, Ciclomed, Erasca, Evelo Biosciences, Exelexis, G1 Therapeutics, GlaxoSmithKline GSK, IGM Biosciences, Incyte, Isofol, Klus Pharma, Macrogenics, Merck Co, Mersana Therapeutics, OncoMed Pharmaceuticals, Pfizer, Regeron Pharmaceuticals, Revolution Medicines, Synermore Biologics Co, Takeda, Tarveda Therapeutics, Tesaro, Tempest Therapeutics, and Vigeo Therapeutics Inc outside the submitted work. Dr Chon reported grants from Roche, Bayer, Celgene Cancer Care Links, AstraZeneca, Ono Pharma Korea, Eisai, Sanofi, Servier, MSD Oncology, Menarini, BMS, Sillajen, and GreenCross Cell outside the submitted work. Dr Hsu reported grants from China Medical University Hospital, and the National Science Council outside the submitted work. Dr Cammà reported personal fees from Roche, Eisai, AstraZeneca, and AbbVie outside the submitted work. Dr Giannini reported personal fees from Roche, AstraZeneca, and Eisai-MSD during the conduct of the study. Dr Cortellini reported personal fees from MSD, BMS, Roche, Regeneron, Sanofi, GSK, OncoC4, and AstraZeneca outside the submitted work. Dr Pinato reported personal fees from Roche, Astra Zeneca, Eisai, Mina Therapeutics, Starpharma, Lift Biosciences, Boston Scientific, and Avamune and grants from GSK, MSD, BMS outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Overall Survival (OS) in the Best Supportive Care (BSC) and Immune Checkpoint Inhibitor (ICI)–Exposed Inverse Probability of Treatment Weighting Populations
B, Stratified according to the type of treatment (nivolumab and atezolizumab + bevacizumab [A+B]). HR indicates hazard ratio.
See this image and copyright information in PMC

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