Impact of Frequent Immune‐Mediated Adverse Events on Treatment Continuity and Outcomes During Durvalumab Plus Tremelimumab Therapy for Unresectable Hepatocellular Carcinoma

ABSTRACT Durvalumab plus tremelimumab (Dur/Tre) is the first‐line treatment for unresectable hepatocellular carcinoma (uHCC). Immune‐mediated adverse events (imAEs) are common; however, the impact of specific imAE types on treatment persistence and outcomes remains unclear. This study evaluated the clinical features and prognostic implications of common imAEs during Dur/Tre therapy. This multicenter retrospective analysis included 351 patients with uHCC treated with Dur/Tre (January 2023 and February 2025), of whom 69 developed imAEs and had a follow up period of > 1 month. Baseline characteristics, period to onset and severity of imAEs, corticosteroid use, treatment continuation and subsequent therapies, progression‐free survival (PFS) and overall survival (OS) were analyzed according to imAE types. Among 69 patients, 34 developed colitis, 19 developed hepatitis and 16 developed endocrine disorders. The median age was 72 years, with 13% classified as Child‐Pugh B. The median period to imAE onset was 0.75 months (interquartile range, 0.38–1.25). Steroids at a dose equivalent to > 20 mg of prednisolone were administered to 46 patients (66.7%). Two‐thirds of the patients continued Dur/Tre despite imAE onset. Colitis occurred the earliest (median 0.54 months) and had the highest steroid requirement (82.4%), frequently resulting in treatment interruption. Endocrine disorders showed the highest continuation rate (75%). Although not statistically significant in PFS (median 11.2 months: 95% CI, 1.96–not achieved (NA), p = 0.450) and OS (95% CI, NA–NA, p = 0.134), compared with colitis (PFS; 4.3 months, OS; not reached) and hepatitis (PFS; 3.4 months, OS: 14.6 months). These findings should be interpreted cautiously given the small sample size. Subsequent systemic or locoregional therapies, including tyrosine kinase inhibitors, atezolizumab plus bevacizumab and interventional therapies, were administered to more than 65% of the patients. In Dur/Tre therapy, imAE impact varied by type; endocrine disorders are linked to better treatment continuation and prognosis, whereas colitis and hepatitis often lead to treatment interruption. Trial Registration: Takasaki General Medical Center (IRB No. TGMC2024–03)

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Journal
Liver international communications.
Published
2026-04-01
DOI
https://doi.org/10.1002/lci2.70042
Primary Topic
Hepatocellular Carcinoma Treatment and Prognosis
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article
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article

Impact of Frequent Immune‐Mediated Adverse Events on Treatment Continuity and Outcomes During Durvalumab Plus Tremelimumab Therapy for Unresectable Hepatocellular Carcinoma

Hideko Ohama, Norio Itokawa, Hironori Tanaka, Kazunari Tanaka et al.
Liver international communications.
Hepatocellular Carcinoma Treatment and Prognosis
article

Impact of Frequent Immune‐Mediated Adverse Events on Treatment Continuity and Outcomes During Durvalumab Plus Tremelimumab Therapy for Unresectable Hepatocellular Carcinoma

Hideko Ohama, Norio Itokawa, Hironori Tanaka, Kazunari Tanaka, Yuki Kanayama, Hidenao Noritake, Kazuya Kariyama, Hirayuki Enomoto, Kazuhiro Nouso, Hideyuki Tamai, Shinya Fukunishi, Takuya Nagano, Ei Itobayashi, Hisashi Kosaka, Yutaka Yata, Yuichi Koshiyama, Fujimasa Tada, Kosuke Matsui, Yoshihide Ueda, the RELPEC Group and HCC 48 Group, Chikara Ogawa, Takumi Fukumoto, Yoichi Hiasa, Michitaka Imai, Toru Ishikawa, Masanori Atsukawa, Masashi Hirooka, Taeang Arai, Tomoko Aoki, Hiroki Nishikawa, Tomomitsu Matono, Kunihiko Tsuji, Hidekatsu Kuroda, Shohei Komatsu, Joji Tani, Takeshi Hatanaka, Asahiro Morishita, Masaki Kaibori, Koichi Takaguchi, Akemi Tsutsui, Atsushi Hiraoka, Hidenori Toyoda, Takashi Kumada, Hironori Ochi, Takashi Nishimura, Atsushi Naganuma, Takanori Matsuura, Satoru Kakizaki, Kazuto Tajiri, Toshifumi Tada, Masatoshi Kudo, Tomomi Okubo, Kazuhito Kawata, Shinichiro Nakamura
article en

Abstract

ABSTRACT Durvalumab plus tremelimumab (Dur/Tre) is the first‐line treatment for unresectable hepatocellular carcinoma (uHCC). Immune‐mediated adverse events (imAEs) are common; however, the impact of specific imAE types on treatment persistence and outcomes remains unclear. This study evaluated the clinical features and prognostic implications of common imAEs during Dur/Tre therapy. This multicenter retrospective analysis included 351 patients with uHCC treated with Dur/Tre (January 2023 and February 2025), of whom 69 developed imAEs and had a follow up period of > 1 month. Baseline characteristics, period to onset and severity of imAEs, corticosteroid use, treatment continuation and subsequent therapies, progression‐free survival (PFS) and overall survival (OS) were analyzed according to imAE types. Among 69 patients, 34 developed colitis, 19 developed hepatitis and 16 developed endocrine disorders. The median age was 72 years, with 13% classified as Child‐Pugh B. The median period to imAE onset was 0.75 months (interquartile range, 0.38–1.25). Steroids at a dose equivalent to > 20 mg of prednisolone were administered to 46 patients (66.7%). Two‐thirds of the patients continued Dur/Tre despite imAE onset. Colitis occurred the earliest (median 0.54 months) and had the highest steroid requirement (82.4%), frequently resulting in treatment interruption. Endocrine disorders showed the highest continuation rate (75%). Although not statistically significant in PFS (median 11.2 months: 95% CI, 1.96–not achieved (NA), p = 0.450) and OS (95% CI, NA–NA, p = 0.134), compared with colitis (PFS; 4.3 months, OS; not reached) and hepatitis (PFS; 3.4 months, OS: 14.6 months). These findings should be interpreted cautiously given the small sample size. Subsequent systemic or locoregional therapies, including tyrosine kinase inhibitors, atezolizumab plus bevacizumab and interventional therapies, were administered to more than 65% of the patients. In Dur/Tre therapy, imAE impact varied by type; endocrine disorders are linked to better treatment continuation and prognosis, whereas colitis and hepatitis often lead to treatment interruption. Trial Registration: Takasaki General Medical Center (IRB No. TGMC2024–03)

Liver international communications.Vol. 7(2)
Kansai Medical University (JP), Iwate Medical University (JP), Kagawa University (JP), Hamamatsu University School of Medicine (JP), Wakayama Rosai Hospital (JP), Niigata Cancer Center Hospital (JP), Takamatsu Red Cross Hospital (JP), Saiseikai Niigata Daini Hospital (JP), National Hospital Organization Takasaki Medical Center (JP), Matsuyama Red Cross Hospital (JP), Ogaki Municipal Hospital (JP), Himeji Medical Center (JP), Hanwa Memorial Hospital (JP), Gunma Saiseikai Maebashi Hospital (JP), Himeji Red Cross Hospital (JP), Teine Keijinkai Hospital (JP), Asahi General Hospital (JP), Toyama University Hospital (JP), Ehime Prefectural Central Hospital (JP), Kagawa Prefectural Central Hospital (JP), Takarazuka City Hospital (JP), Ehime University (JP), Gifu Kyoritsu University (JP), Kobe University (JP), Nippon Medical School (JP), Hyogo University (JP), Osaka University of Pharmaceutical Sciences (JP), Kindai University (JP)
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Hepatocellular Carcinoma Treatment and Prognosis
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