Second-Line Practices in the Era of Immunotherapy in HCC: The CHIEF Cohort
Abstract
Background & aims: Unresectable hepatocellular carcinoma (HCC) remains a major global health burden. Immunotherapy-based combinations have become the standard of care in first-line (1L) treatment, but evidence on subsequent therapies is limited. This study aimed to describe access to and outcomes of second-line (2L) treatments following atezolizumab-bevacizumab (AB) compared with sorafenib (Sor), using real-world data from the French prospective CHIEF cohort. Methods: Patients were included in the CHIEF cohort, part of the prospective, real-world STRETCH study (Systemic Treatment SEquences in patients with unresectable HCC). Adults with unresectable HCC who received 1L treatment with AB or Sor between September 2019 and September 2024 were analyzed. Median overall survival (mOS) and median progression-free survival (mPFS) were calculated from 2L initiation. Results: Among 1,103 patients included (AB, n = 899; Sor, n = 204), baseline characteristics were broadly similar, with most patients having Child-Pugh A liver function (77.1% vs. 70.3%) and Barcelona Clinic Liver Cancer (BCLC) stage C disease (66.3% vs. 84.3%). mOS was 22.3 months [95% CI, 18.5-27.4] with AB and 9.4 months [7.3-12.7] with Sor (p < 0.0001). Following progression, 42.1% of AB-treated and 60.0% of Sor-treated patients received 2L (p < 0.001). After AB, 70.8% received tyrosine kinase inhibitors (TKIs) with a mOS of 13.0 months [9.8-15.5]; survival was not reached for patients receiving immunotherapy or combination regimens (p = 0.0009). mOS with 2L TKIs was similar after AB or Sor (13.0 vs. 8.6 months; p = 0.082). Conclusions: In this prospective real-world cohort, access to 2L treatment was lower after AB than Sor. Nonetheless, 2L TKIs achieved numerically similar survival outcomes irrespective of 1L therapy, while immunotherapy rechallenge yielded encouraging results in selected patients. Impact and implications: The increasing use of immunotherapy-based combinations in first-line treatment for unresectable hepatocellular carcinoma raises crucial questions about optimal sequencing strategies after progression. This study provides prospective, real-world evidence on second-line treatment access and outcomes in the post-immunotherapy setting. These findings are important for clinicians and researchers seeking to refine treatment algorithms and ensure equitable access to effective therapies. In practice, the numerically similar survival achieved with tyrosine kinase inhibitors across treatment sequences and the promising results of immunotherapy rechallenge may inform individualized patient management and guide the design of future clinical trials evaluating sequential strategies.
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BibTeX
@article{decraecker2026secondline,
title = {{Second-Line Practices in the Era of Immunotherapy in HCC: The CHIEF Cohort}},
author = {Marie Decraecker and Héloïse Bourien and Elhadji Malick Thiam and Julien Edeline and Alice Koudjou-Sonegueng and Philippe Merle and Jean-Frédéric Blanc and Giuliana Amaddeo and Thomas Uguen and Thomas Decaens and Nathalie Ganne-Carrie and Christine Silvain and Mohamed Bouattour and Ghassan Riachi and Manon Allaire and Stéphane Cattan and Xavier Adhoute and Marilyne Gratien and Rodolphe Anty and Jean-Marie Peron and Fréderic Oberti and Aurore Baron and Alina Pascale and Georges-Philippe Pageaux and Sylvain Manfredi and Jean-Baptiste Nousbaum and Marie Lequoy and Anaïs Jaillais and Isabelle Ollivier-Hourmand and Moana Gelu-Simeon and Jean-Pierre Bronowicki and Alexandra Heurgue and Anne-Laure Villing and Isabelle Rosa and Jean-François Cadranel and Gérard Ducournau and Olivier Ganry and Charlotte Costentin and Eric Nguyen-Khac},
journal = {JHEP Reports Innovation in Hepatology},
year = {2026},
month = oct,
doi = {10.1016/j.jhepr.2026.101904},
url = {https://u-picardie.hal.science/hal-05657205v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Second-Line Practices in the Era of Immunotherapy in HCC: The CHIEF Cohort
AU - Marie Decraecker
AU - Héloïse Bourien
AU - Elhadji Malick Thiam
AU - Julien Edeline
AU - Alice Koudjou-Sonegueng
AU - Philippe Merle
AU - Jean-Frédéric Blanc
AU - Giuliana Amaddeo
AU - Thomas Uguen
AU - Thomas Decaens
AU - Nathalie Ganne-Carrie
AU - Christine Silvain
AU - Mohamed Bouattour
AU - Ghassan Riachi
AU - Manon Allaire
AU - Stéphane Cattan
AU - Xavier Adhoute
AU - Marilyne Gratien
AU - Rodolphe Anty
AU - Jean-Marie Peron
AU - Fréderic Oberti
AU - Aurore Baron
AU - Alina Pascale
AU - Georges-Philippe Pageaux
AU - Sylvain Manfredi
AU - Jean-Baptiste Nousbaum
AU - Marie Lequoy
AU - Anaïs Jaillais
AU - Isabelle Ollivier-Hourmand
AU - Moana Gelu-Simeon
AU - Jean-Pierre Bronowicki
AU - Alexandra Heurgue
AU - Anne-Laure Villing
AU - Isabelle Rosa
AU - Jean-François Cadranel
AU - Gérard Ducournau
AU - Olivier Ganry
AU - Charlotte Costentin
AU - Eric Nguyen-Khac
PY - 2026
DA - 2026/10/13
JO - JHEP Reports Innovation in Hepatology
DO - 10.1016/j.jhepr.2026.101904
UR - https://u-picardie.hal.science/hal-05657205v1
AB - Background & aims: Unresectable hepatocellular carcinoma (HCC) remains a major global health burden. Immunotherapy-based combinations have become the standard of care in first-line (1L) treatment, but evidence on subsequent therapies is limited. This study aimed to describe access to and outcomes of second-line (2L) treatments following atezolizumab-bevacizumab (AB) compared with sorafenib (Sor), using real-world data from the French prospective CHIEF cohort. Methods: Patients were included in the CHIEF cohort, part of the prospective, real-world STRETCH study (Systemic Treatment SEquences in patients with unresectable HCC). Adults with unresectable HCC who received 1L treatment with AB or Sor between September 2019 and September 2024 were analyzed. Median overall survival (mOS) and median progression-free survival (mPFS) were calculated from 2L initiation. Results: Among 1,103 patients included (AB, n = 899; Sor, n = 204), baseline characteristics were broadly similar, with most patients having Child-Pugh A liver function (77.1% vs. 70.3%) and Barcelona Clinic Liver Cancer (BCLC) stage C disease (66.3% vs. 84.3%). mOS was 22.3 months [95% CI, 18.5-27.4] with AB and 9.4 months [7.3-12.7] with Sor (p < 0.0001). Following progression, 42.1% of AB-treated and 60.0% of Sor-treated patients received 2L (p < 0.001). After AB, 70.8% received tyrosine kinase inhibitors (TKIs) with a mOS of 13.0 months [9.8-15.5]; survival was not reached for patients receiving immunotherapy or combination regimens (p = 0.0009). mOS with 2L TKIs was similar after AB or Sor (13.0 vs. 8.6 months; p = 0.082). Conclusions: In this prospective real-world cohort, access to 2L treatment was lower after AB than Sor. Nonetheless, 2L TKIs achieved numerically similar survival outcomes irrespective of 1L therapy, while immunotherapy rechallenge yielded encouraging results in selected patients. Impact and implications: The increasing use of immunotherapy-based combinations in first-line treatment for unresectable hepatocellular carcinoma raises crucial questions about optimal sequencing strategies after progression. This study provides prospective, real-world evidence on second-line treatment access and outcomes in the post-immunotherapy setting. These findings are important for clinicians and researchers seeking to refine treatment algorithms and ensure equitable access to effective therapies. In practice, the numerically similar survival achieved with tyrosine kinase inhibitors across treatment sequences and the promising results of immunotherapy rechallenge may inform individualized patient management and guide the design of future clinical trials evaluating sequential strategies.
SN - 2589-5559
ER -