Long-term survival and cure fraction in patients with advanced hepatocellular carcinoma under immunotherapy in randomized controlled trials and real-world data

BACKGROUND & AIMS: Immune checkpoint inhibitors (ICIs) can induce long-term survival and even cancer cure in several cancers. Mixture cure models (MCMs) estimate the fraction of long-term survivors and cured patients but have not been applied in HCC. METHODS: We identified phase 3 randomized trials of first-line ICI in advanced HCC with mature follow-up (≥30 months) and analyzed a cohort of HCC patients treated with atezolizumab-bevacizumab. After reconstructing Kaplan-Meier curves, MCMs estimated long-term survivors' fraction (overall survival, OS) and cure fractions (progression-free survival, PFS). RESULTS: In HIMALAYA (median follow-up of 60 months), long-term survival was 12.8% (95%CI:8.5-18.6%) with durvalumab-tremelimumab versus 5.2% (95%CI:2.6-10.2%) with sorafenib; cure fraction was not assessable.In CheckMate9DW (median follow-up: 35.2 month), long-term survival was 8.7% (95%CI:0.2-81.3%) versus 4.1% (95%CI:0.1-66.1%) and cure fractions were 17.8% (95%CI:12.0-25.8%) versus 3.5% (95%CI:0.7-16.7%) for nivolumab-ipilimumab and sorafenib/lenvatinib respectively with long-term OS estimates remaining exploratory due to limited late numbers at risk.In RATIONALE-301, long-term survival was 25.2% (95%CI:19.2-32.2) with tislelizumab versus 15.4% (95%CI: 10.0-22.8) with sorafenib. IMbrave150 trial was not analyzed due to insufficient follow-up (15.6 months). Among a clinical cohort of 1581 patients treated by atezolizumab-bevacizumab (median follow-up: 34.7 months), long-term survival was 12.3% (95%CI:9.3-16.1%) and cure fraction 7.9% (95%CI:6.3-9.8%). In 1187 patients meeting IMbrave150 criteria, long-term survival reached 15.4% (95%CI:10.6-18.5%) and cure fraction 9.1% (95%CI:7.3-11.4%).ALBI score, and hepatitis C predicted long-term survival and albumin and hepatitis C predicted cure. CONCLUSION: Across trials and real-world data, ICIs combinations achieve long-term survival in 10-15% of advanced HCC patients, with cure fractions of 7-9%.

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Journal
Clinical Cancer Research
Published
2026-04-20
DOI
https://doi.org/10.1158/1078-0432.ccr-25-4943
Primary Topic
Hepatocellular Carcinoma Treatment and Prognosis
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article
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article

Long-term survival and cure fraction in patients with advanced hepatocellular carcinoma under immunotherapy in randomized controlled trials and real-world data

Dominique Thabut, Massih Ningarhari, Rohini Sharma, Jean‐Charles Nault et al.
Clinical Cancer Research
Hepatocellular Carcinoma Treatment and Prognosis
article

Long-term survival and cure fraction in patients with advanced hepatocellular carcinoma under immunotherapy in randomized controlled trials and real-world data

Dominique Thabut, Massih Ningarhari, Rohini Sharma, Jean‐Charles Nault, Han Chu Lee, Hélène Regnault, Clémence Hollande, Sabrina Sidali, Claudia Campani, Isabelle Ollivier‐Hourmand, Jihyun An, Manon Allaire, Marie Lequoy, Pierre Nahon, Alina Pascale, Fabio Marra, Nathalie Ganne‐Carrié, Giuliana Amaddeo, Yann Touchefeu, Maxime Ronot, Victoria Delhoume, Chloé Metivier, Ju Hyun Shim, Jean-Marie Peron, Line Ntandaja-Wandji, Mohamed Bouattour, Paris Liver Cancer Group, Violaine Ozenne
article en

Abstract

BACKGROUND & AIMS: Immune checkpoint inhibitors (ICIs) can induce long-term survival and even cancer cure in several cancers. Mixture cure models (MCMs) estimate the fraction of long-term survivors and cured patients but have not been applied in HCC. METHODS: We identified phase 3 randomized trials of first-line ICI in advanced HCC with mature follow-up (≥30 months) and analyzed a cohort of HCC patients treated with atezolizumab-bevacizumab. After reconstructing Kaplan-Meier curves, MCMs estimated long-term survivors' fraction (overall survival, OS) and cure fractions (progression-free survival, PFS). RESULTS: In HIMALAYA (median follow-up of 60 months), long-term survival was 12.8% (95%CI:8.5-18.6%) with durvalumab-tremelimumab versus 5.2% (95%CI:2.6-10.2%) with sorafenib; cure fraction was not assessable.In CheckMate9DW (median follow-up: 35.2 month), long-term survival was 8.7% (95%CI:0.2-81.3%) versus 4.1% (95%CI:0.1-66.1%) and cure fractions were 17.8% (95%CI:12.0-25.8%) versus 3.5% (95%CI:0.7-16.7%) for nivolumab-ipilimumab and sorafenib/lenvatinib respectively with long-term OS estimates remaining exploratory due to limited late numbers at risk.In RATIONALE-301, long-term survival was 25.2% (95%CI:19.2-32.2) with tislelizumab versus 15.4% (95%CI: 10.0-22.8) with sorafenib. IMbrave150 trial was not analyzed due to insufficient follow-up (15.6 months). Among a clinical cohort of 1581 patients treated by atezolizumab-bevacizumab (median follow-up: 34.7 months), long-term survival was 12.3% (95%CI:9.3-16.1%) and cure fraction 7.9% (95%CI:6.3-9.8%). In 1187 patients meeting IMbrave150 criteria, long-term survival reached 15.4% (95%CI:10.6-18.5%) and cure fraction 9.1% (95%CI:7.3-11.4%).ALBI score, and hepatitis C predicted long-term survival and albumin and hepatitis C predicted cure. CONCLUSION: Across trials and real-world data, ICIs combinations achieve long-term survival in 10-15% of advanced HCC patients, with cure fractions of 7-9%.

Clinical Cancer Research
Hôpital Beaujon (FR), Asan Medical Center (KR), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire Henri-Mondor (FR), Centre Hospitalier Universitaire de Toulouse (FR), Sorbonne Université (FR), University of Ulsan (KR), Centre de Recherche des Cordeliers (FR), Hopitaux Civils de Colmar (FR), Assistance Publique – Hôpitaux de Paris (FR), Hôpital Saint-Antoine (FR), NIHR Imperial Biomedical Research Centre (GB), Centre Hospitalier Universitaire de Caen Normandie (FR), Pitié-Salpêtrière Hospital (FR), Hanyang University Guri Hospital (KR), Hôpitaux Universitaires Henri-Mondor (FR), Hôpital Jean-Verdier (FR), Hôpital Paul-Brousse (FR), University of Florence (IT), Imperial College London (GB), Nantes Université (FR)
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Openalex Percentile: Top 25%
Hepatocellular Carcinoma Treatment and Prognosis
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