Clinical outcomes of PD-1/PD-L1 inhibitors in patients with advanced hepatocellular carcinoma: a systematic review and meta-analysis

Wen, Wen; Zhang, Yong; Zhang, Hua; Chen, Yingshuang

doi:10.1007/s00432-022-04057-3

Cited by 14 publications

(9 citation statements)

References 47 publications

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“…Furthermore, other immune-based combination strategies have been shown to prolong OS and PFS and increase the rates of CR and PR, as confirmed by a meta-analysis conducted by Rizzo et al ( 19 ). A multitude of contemporary studies have also substantiated that immune-based combinations are a viable approach for the management of advanced HCC ( 20 , 21 ). Currently, in the absence of direct comparisons between first-line immune-based therapies, clinicians must judiciously select treatments based on nuanced inclusion criteria and demographics across different clinical trials, factoring not only drug efficacy but also a spectrum of variables, including adverse drug reactions, patient comorbidities, and pharmacoeconomics.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of PD-1/PD-L1 inhibitor-based immune combination therapy versus sorafenib in the treatment of advanced hepatocellular carcinoma: a meta-analysis

She,

Wu,

Cheng

et al. 2024

Front. Med.

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ObjectiveTo systematically evaluate the safety and efficacy of PD-1/PD-L1 inhibitor-based immunotherapy (hereafter referred to as “combination immunotherapy”) compared with that of sorafenib in the treatment of hepatocellular carcinoma (HCC).MethodsDatabases such as PubMed, Embase, and the Cochrane Library were searched from the date of their establishment to September 2023 to identify randomized controlled trials (RCTs) of combination immunotherapy versus sorafenib for the treatment of advanced HCC. Two reviewers independently evaluated the quality of the included studies, extracted the data, and cross-checked the information. The meta-analysis was performed using RevMan 5.3 software.ResultsA total of 5 RCTs were included. The results of the meta-analysis showed the following: (1) Effectiveness. Compared to sorafenib, combination immunotherapy significantly improved overall survival (OS, HR = 0.69, 95% CI: 0.58 ~ 0.82, p < 0.01) and progression-free survival (PFS, HR = 0.62, 95% CI: 0.50 ~ 0.78, p < 0.001) in patients with advanced HCC. (2) Safety. Both groups had comparatively high incidences of adverse events (AEs), but the difference in any treatment-related adverse events was not significant between the two arms (OR = 0.98, 95% CI: 0.95 ~ 1.02, p = 0.34). The difference in the incidence of grade 1–2 adverse reactions was statistically significant (OR = 0.66, 95% CI = 0.49–0.90, p = 0.001). There were no differences in grade 3/4 TRAEs or grade 5 TRAEs (OR = 1.46, 95% CI = 0.78 ~ 2.71, p = 0.24; OR = 1.08, 95% CI = 0.73 ~ 1.58, p = 0.71).ConclusionCombined immunotherapy can significantly prolong the OS and PFS of patients with advanced HCC without increasing the incidence of adverse effects in terms of safety, but the incidence of AEs in different systems is different.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of PD-1/PD-L1 inhibitor-based immune combination therapy versus sorafenib in the treatment of advanced hepatocellular carcinoma: a meta-analysis

She,

Wu,

Cheng

et al. 2024

Front. Med.

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“…After the up-regulation of PD-1, HBV-speci c CD8 + T lymphocytes are in a highly depleted and hypofunctional state. Therefore, PD-1/PD-L1 immune checkpoint inhibitors (ICIs) become a new approach to treat hepatocellular carcinoma [32,33]. As we all know, immune escape exerts a critical effect on HNC occurrence and development, thus immunotherapy is a good choice.…”

Section: Discussionmentioning

confidence: 99%

Association of hepatitis B virus infection with head and neck cancer: a propensity-matched study

Zhang

Wang

2023

Preprint

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Objective This work focused on investigating the relation between hepatitis B virus (HBV) infection with head and neck cancer (HNC), identifying the associated risk factors and providing a reference for preventing and treating HNC. Methods Retrospective analysis was conducted on 1,572 HNC cases who were hospitalized between January 2009 and December 2020. Meanwhile, 58,409 individuals with non-oncological illnesses from the departments of oral and maxillofacial surgery, psychiatry, neurology and cardiology were recruited as controls. R software was utilized for data processing. Clinical data were processed using SPSS 22.0, while baseline radiotherapy data were balanced with 1:4 propensity score matching (PSM). Results In this study, 1:4 PSM was completed in 1,572 HNC patients and 6,288 controls. In comparison with controls, HNC cases had a markedly increased HBsAg positivity rate (5.9% vs 3.5%, p<0.001). Additionally, the HBsAb positivity rate of HNC cases remarkably decreased relative to controls (52.9% vs 58.7%, p<0.001). Conclusions HBV infection was positively related to HNC, while HBsAb was negatively correlated with HNC.

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“…All these result suggestted that high-LRRS may relate to immunosuppression, and associate with a poor prognosis,while low-LRRS maybe relate to immune activity and achieve a well prognosis. Nowadays, a series of targeting drugs have been developed for HCC such as, anti-PD-1, anti-PD-L1 and anti-CTLA-4 63 . However, some success has been reported with immunotherapy in the treatment of HCC, the number of people who benefited from immunotherapy is still very low.…”

Section: Discussionmentioning

confidence: 99%

Construction and validation of a novel lysosomal signature for hepatocellular carcinoma prognosis, diagnosis, and therapeutic decision-making

Chen,

Gao,

et al. 2023

Sci Rep

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Lysosomes is a well-recognized oncogenic driver and chemoresistance across variable cancer types, and has been associated with tumor invasiveness, metastasis, and poor prognosis. However, the significance of lysosomes in hepatocellular carcinoma (HCC) is not well understood. Lysosomes-related genes (LRGs) were downloaded from Genome Enrichment Analysis (GSEA) databases. Lysosome-related risk score (LRRS), including eight LRGs, was constructed via expression difference analysis (DEGs), univariate and LASSO-penalized Cox regression algorithm based on the TCGA cohort, while the ICGC cohort was obtained for signature validation. Based on GSE149614 Single-cell RNA sequencing data, model gene expression and liver tumor niche were further analyzed. Moreover, the functional enrichments, tumor microenvironment (TME), and genomic variation landscape between LRRSlow/LRRShigh subgroup were systematically investigated. A total of 15 Lysosomes-related differentially expressed genes (DELRGs) in HCC were detected, and then 10 prognosis DELRGs were screened out. Finally, the 8 optimal DELRGs (CLN3, GBA, CTSA, BSG, APLN, SORT1, ANXA2, and LAPTM4B) were selected to construct the LRRS prognosis signature of HCC. LRRS was considered as an independent prognostic factor and was associated with advanced clinicopathological features. LRRS also proved to be a potential marker for HCC diagnosis, especially for early-stage HCC. Then, a nomogram integrating the LRRS and clinical parameters was set up displaying great prognostic predictive performance. Moreover, patients with high LRRS showed higher tumor stemness, higher heterogeneity, and higher genomic alteration status than those in the low LRRS group and enriched in metabolism-related pathways, suggesting its underlying role in the progression and development of liver cancer. Meanwhile, the LRRS can affect the proportion of immunosuppressive cell infiltration, making it a vital immunosuppressive factor in the tumor microenvironment. Additionally, HCC patients with low LRRS were more sensitive to immunotherapy, while patients in the high LRRS group responded better to chemotherapy. Upon single-cell RNA sequencing, CLN3, GBA, and LAPTM4B were found to be specially expressed in hepatocytes, where they promoted cell progression. Finally, RT-qPCR and external datasets confirmed the mRNA expression levels of model genes. This study provided a direct links between LRRS signature and clinical characteristics, tumor microenvironment, and clinical drug-response, highlighting the critical role of lysosome in the development and treatment resistance of liver cancer, providing valuable insights into the prognosis prediction and treatment response of HCC, thereby providing valuable insights into prognostic prediction, early diagnosis, and therapeutic response of HCC.

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Clinical outcomes of PD-1/PD-L1 inhibitors in patients with advanced hepatocellular carcinoma: a systematic review and meta-analysis

Cited by 14 publications

References 47 publications

Efficacy and safety of PD-1/PD-L1 inhibitor-based immune combination therapy versus sorafenib in the treatment of advanced hepatocellular carcinoma: a meta-analysis

Efficacy and safety of PD-1/PD-L1 inhibitor-based immune combination therapy versus sorafenib in the treatment of advanced hepatocellular carcinoma: a meta-analysis

Association of hepatitis B virus infection with head and neck cancer: a propensity-matched study

Construction and validation of a novel lysosomal signature for hepatocellular carcinoma prognosis, diagnosis, and therapeutic decision-making

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