Efficacy and safety of immune checkpoint inhibitors for hepatocellular carcinoma patients with macrovascular invasion or extrahepatic spread: a systematic review and meta-analysis of 54 studies with 6187 hepatocellular carcinoma patients

Han, Chen; Tian, Bao-Wen; Yan, Lun-Jie; Ding, Zi-Niu; Liu, Hui; Mao, Xin-Cheng; Tian, Jin-Cheng; Xue, Jun-Shuai; Tan, Siyu; Dong, Zhao‐Ru; Yan, Yu-Chuan; Hong, Jian‐Guo; Chen, Zhiqiang; Wang, Dongxu; Li, Tao

doi:10.1007/s00262-023-03390-x

Cited by 6 publications

(3 citation statements)

References 78 publications

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“…Similarly, patients with ECOG 1 treated with immunotherapy combined with anti-angiogenetic agents have also demonstrated favorable survival benefits (HR = 0.56 and 0.59, respectively). While initial concerns regarding the OS response of patients with EHS to immune checkpoint inhibitors (ICIs) persisted [ 18 ], recent phase III clinical studies have consistently shown improved OS outcomes in this patient population [ 3 , 19 ]. Furthermore, a comparative analysis of ICIs treatments has revealed that patients with EHS exhibit preferential OS responses when treated with immunotherapy combined with anti-angiogenetic agents.…”

Section: Discussionmentioning

confidence: 99%

Efficacy comparison of immune combination therapies in subgroups for advanced hepatocellular carcinoma patients: Systematic review and network meta-analysis

Wang,

Lau,

et al. 2024

PLoS ONE

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Background There is a lack of precision in the immunotherapy strategy tailored for patients exhibiting diverse clinical characteristics. This study aims to employ a rigorous network meta-analysis (NMA) approach to systematically evaluate the effectiveness of immune-combination therapies among patients with advanced hepatocellular carcinoma, taking into account their varying clinico-characteristics. Methods Studies were retrieved from PubMed, Embase, Cochrane Library, and Web of Science databases. The included first-line phase III studies were categorized into three types: immunotherapy combined with anti-angiogenetic agents, immunotherapy combined with tyrosine kinase inhibitors, and dual immunotherapy, with sorafenib serving as the control group. The primary endpoint used to assess efficacy was overall survival (OS), facilitating a comparative analysis among the three treatment modalities. Furthermore, subgroup analyses were conducted to evaluate the varying effectiveness for patients with diverse clinico-characteristics. Secondary outcome measures included progression-free survival, objective response rate, and toxicity assessment. Results A total of 6 studies were included in the NMA, encompassing a cohort of 3840 patients. The results revealed that immunotherapy combined with anti-angiogenetic agents exhibited a significantly enhanced therapeutic effect in terms of improving OS compared to sorafenib (HR = 0.61, 95% CrI, 0.42–0.90). Furthermore, based on various clinicopathological features, this combination therapy demonstrated superior OS responses in specific patient subgroups: BCLC C (HR = 0.63, 95% CrI, 0.42–0.93), ECOG 1 (HR = 0.57, 95% CrI, 0.36–0.91), with extrahepatic spread (EHS) (HR = 0.59, 95% CrI, 0.37–0.92), alpha fetoprotein (AFP)<400ng/ml (HR = 0.56, 95% CrI, 0.33–0.94) and viral hepatitis positivity (HR = 0.56, 95% CrI, 0.39–0.77) (especially HBV (HR = 0.58, 95% CrI, 0.40–0.85)). Importantly, the advantage of this combination therapy was even more pronounced in patients with viral hepatitis positivity. Also, the adverse events associated with immunotherapy combined with antiangiogenic drugs were moderate. Conclusions Immunotherapy combined with anti-angiogenetic agents could represent the most effective first-line intervention for achieving improved OS, particularly in patients with viral hepatitis positivity.

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Section: Discussionmentioning

confidence: 99%

Efficacy comparison of immune combination therapies in subgroups for advanced hepatocellular carcinoma patients: Systematic review and network meta-analysis

Wang,

Lau,

et al. 2024

PLoS ONE

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“…The presence of metastasis, which indicates that the tumor has spread to other parts of the body, has been identified as an independent risk factor for inferior OS in patients treated with lenvatinib monotherapy or lenvatinib plus ICI (60). Additionally, the presence of extrahepatic spread (metastasis outside the liver) has been associated with an inferior ORR in ICIs-treated HCC patients (102). Macrovascular invasion, which refers to tumor thrombosis in the portal vein or hepatic vein, has also been associated with poorer PFS and OS (102).…”

Section: Clinical Indicators Of Tumormentioning

confidence: 99%

“…Additionally, the presence of extrahepatic spread (metastasis outside the liver) has been associated with an inferior ORR in ICIs-treated HCC patients (102). Macrovascular invasion, which refers to tumor thrombosis in the portal vein or hepatic vein, has also been associated with poorer PFS and OS (102). In a retrospective study involving 604 HCC patients treated with ICIs after progression, intrahepatic growth, and new vascular invasion were associated with a poorer prognosis (103).…”

Section: Clinical Indicators Of Tumormentioning

confidence: 99%

Biomarkers predicting the efficacy of immune checkpoint inhibitors in hepatocellular carcinoma

Qin,

Jin,

2023

Front. Immunol.

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In recent years, immune checkpoint inhibitors (ICIs) have emerged as a transformative approach in treating advanced hepatocellular carcinoma (HCC). Despite their success, challenges persist, including concerns about their effectiveness, treatment costs, frequent occurrence of treatment-related adverse events, and tumor hyperprogression. Therefore, it is imperative to identify indicators capable of predicting the efficacy of ICIs treatment, enabling optimal patient selection to maximize clinical benefits while minimizing unnecessary toxic side effects and economic losses. This review paper categorizes prognostic biomarkers of ICIs treatment into the following categories: biochemical and cytological indicators, tumor-related markers, imaging and personal features, etiology, gut microbiome, and immune-related adverse events (irAEs). By organizing these indicators systematically, we aim to guide biomarker exploration and inform clinical treatment decisions.

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Clinical spectrum and evolution of immune-checkpoint inhibitors toxicities over a decade—a worldwide perspective

Gougis,

Jochum,

Abbar

et al. 2024

eClinicalMedicine

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Efficacy and safety of immune checkpoint inhibitors for hepatocellular carcinoma patients with macrovascular invasion or extrahepatic spread: a systematic review and meta-analysis of 54 studies with 6187 hepatocellular carcinoma patients

Cited by 6 publications

References 78 publications

Efficacy comparison of immune combination therapies in subgroups for advanced hepatocellular carcinoma patients: Systematic review and network meta-analysis

Efficacy comparison of immune combination therapies in subgroups for advanced hepatocellular carcinoma patients: Systematic review and network meta-analysis

Biomarkers predicting the efficacy of immune checkpoint inhibitors in hepatocellular carcinoma

Clinical spectrum and evolution of immune-checkpoint inhibitors toxicities over a decade—a worldwide perspective

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