Safety and Efficacy of Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Hepatocellular Carcinoma

Yang, Fei; Yang, Jun; Xiang, Wang; Zhong, Bin-Yan; Li, Wan-Ci; Shen, Jian; Zhang, Shuai; Yin, Yuan; Sun, Hongpeng; Wang, Wansheng; Zhu, Xiaoli

doi:10.3389/fonc.2021.657512

Cited by 19 publications

(20 citation statements)

References 35 publications

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“…PFS at 0.5, 1, 1.5, and 2 years were evaluated in 13 ( 21 , 25 , 31 – 38 , 40 – 42 ), 13 ( 21 , 25 , 31 – 38 , 40 – 42 ), 11 ( 21 , 25 , 31 – 37 , 41 , 42 ), and 5 studies ( 21 , 32 , 34 , 37 , 42 ), and the pooled rates and 95%CI were 0.781 (0.688-0.862), 0.387 (0.293-0.486), 0.117 (0.076-0.165), and 0.069 (0.005-0.182), respectively ( Table 3 ). OS at 0.5, 1, 1.5, 2, and 3 years were evaluated in 12 ( 21 , 25 , 31 – 36 , 39 – 42 ), 12 ( 21 , 31 – 34 , 39 – 42 ), 12 ( 21 , 31 – 34 , 39 – 42 ), 9 ( 21 , 31 – 34 , 39 – 42 ), and 5 studies ( 21 , 31 – 33 , 42 ), and the pooled rates and 95%CI were 0.943 (0.902-0.975), 0.690 (0.585-0.786), 0.385 (0.246-0.533), 0.212 (0.117-0.324), and 0.056 (0.028-0.091), respectively ( Table 3 ).…”

Section: Resultsmentioning

confidence: 99%

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The Significance of Transarterial Chemo(Embolization) Combined With Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma in the Era of Systemic Therapy: A Systematic Review

Xin

Fang

et al. 2022

Front. Immunol.

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Background and AimsRegardless of great progress in early detection of hepatocellular carcinoma (HCC), unresectable HCC (uHCC) still accounts for the majority of newly diagnosed HCC with poor prognosis. With the promising results of a double combination of transarterial chemo(embolization) and tyrosine kinase inhibitors (TKIs), and TKIs and immune checkpoint inhibitors (ICIs), a more aggressive strategy, a triple combination of transarterial chemo(embolization), TKIs, and ICIs has been tried in the recent years. Hence, we aimed to conduct a systematic review to verify the safety and efficacy of the triple therapy for uHCC.MethodsPubMed, MedLine, Embase, the Cochrane Library, and Web of Knowledge were used to screen the eligible studies evaluating the clinical efficacy and safety of triple therapy for patients with uHCC up to April 25th 2022, as well as Chinese databases. The endpoints were the complete response (CR), objective response rate (ORR), disease control rate (DCR), conversion rate, progression-free survival (PFS) rate, overall survival (OS) rate, and the incidence of adverse events (AEs).ResultsA total of 15 studies were eligible with 741 patients receiving transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with TKIs and ICIs. The pooled rate and 95% confidence interval (CI) for CR, ORR, and DCR were 0.124 (0.069–0.190), 0.606 (0.528–0.682), and 0.885 (0.835–0.927). The pooled rates for PFS at 0.5 years and 1 year were 0.781 (0.688–0.862) and 0.387 (0.293–0.486), respectively. The pooled rates for OS at 1, 2, and 3 years were 0.690 (0.585–0.786), 0.212 (0.117–0.324), and 0.056 (0.028–0.091), respectively. In addition, the pooled rate and 95%CI for the conversion surgery was 0.359 (0.153–0.595). The subgroup analysis of control studies showed that triple therapy was superior to TACE+TKIs, TKIs+ICIs, and TKIs in CR, ORR, and DCR, conversion rate; PFS; and OS. No fatal AEs were reported, and the top three most common AEs were elevated ALT, elevated AST, and hypertension, as well as severe AEs (grading ≥3).ConclusionWith the current data, we concluded that the triple therapy of TACE/HAIC, TKIs, and ICIs would provide a clinical benefit for uHCC both in short- and long-term outcomes without increasing severe AEs, but the conclusion needs further validation.Systematic Review Registrationhttp://www.crd.york.ac.uk/PROSPERO/, Review registry: CRD42022321970.

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Section: Resultsmentioning

confidence: 99%

“…TACE was adopted in 10 studies ( 21 , 30 – 33 , 38 – 42 ), and HAIC were in 5 studies ( 25 , 34 – 37 ), respectively. Table 4 exhibited the outcomes using TACE+TKIs+ICIs and HAIC+TKIs+ICIs, respectively.…”

Section: Resultsmentioning

confidence: 99%

The Significance of Transarterial Chemo(Embolization) Combined With Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma in the Era of Systemic Therapy: A Systematic Review

Xin

Fang

et al. 2022

Front. Immunol.

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“…Jiang et al have found that metformin triggers the NF-κB signal pathway, which leads to caspase-3/GSDME-mediated cancer cell death [48]. Many recent attempts to increase effectiveness by combining TACE and targeted treatment with immunotherapy have been documented [49][50][51][52]. As a local chemotherapy modality, TACE can promote better immunotherapy by modulating the TIME [50].…”

Section: Discussionmentioning

confidence: 99%

Four-Pyroptosis Gene-Based Nomogram as a Novel Strategy for Predicting the Effect of Immunotherapy in Hepatocellular Carcinoma

Ren

Qin

et al. 2022

BioMed Research International

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Background. Immunotherapy has been considered as a promising cancer treatment for hepatocellular carcinoma (HCC). However, due to the particular immune environment of the liver, identifying patients who could benefit from immunotherapy is critical in clinical practice. Methods. The pyroptosis gene expression database of 54 candidates from The Cancer Genome Atlas (TCGA) were collected to discover the critical prognostic-related pyroptosis genes. A novel pyroptosis gene model was established to calculate the risk score. Kaplan–Meier analysis and receiver operating characteristic curve (ROC) were used to verify its predictive ability. The International Cancer Genome Consortium (ICGC) data was collected as external validation data to verify the model’s accuracy. We employed multiple bioinformatics tools and algorithms to evaluate the tumor immune microenvironment (TIME) and the response to immunotherapy. Results. Our study found that most pyroptosis genes were expressed differently in normal and tumor tissues and that their expression was associated with the prognosis. Then, a precise four-pyroptosis gene model was generated. The one-year area under the curves (AUCs) among the training, internal, and external validation patients were 0.901, 0.727, and 0.671, respectively. An analysis of survival data revealed that individuals had a worse prognosis than patients with low risk. The analysis of TIME revealed that the low-risk group had more antitumor cells, fewer immunosuppressive cells, stronger immune function, less immune checkpoint gene expression, and better immunotherapy response than the high-risk group. Immunophenoscore (IPS) analysis also demonstrated that the low-risk score was related to superior immune checkpoint inhibitors therapy. Conclusion. A nomogram based on the four-pyroptosis gene signature was a novel tool to predict the effectiveness of immunotherapy for HCC. Therefore, individualized treatment targeting the pyroptosis genes may influence TIME and play an essential role in improving the prognosis in HCC patients.

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“…N e v e r t h e l e s s , m o n o t h e r a p i e s w i t h e i t h e r immunotherapeutic agents alone or molecularly targeted drugs alone are not entirely satisfactory (6) (8), which induces a large number of T cells to migrate to the lesion site. This results in high expression of PD-1 molecules on the surface of the T cells, providing more targets for PD-1 inhibitors (30,31).…”

Section: Casementioning

confidence: 99%

“…These combinations have improved the objective response rate of advanced HCC. It may also be possible to increase the efficacy of immunotherapeutic agents synergistically by first performing transarterial chemoembolization (TACE) (7), which can induce the release of large amounts of tumor antigens (8). This may improve patient outcomes and prognosis.…”

Section: Introductionmentioning

confidence: 99%

Complete response by patients with advanced hepatocellular carcinoma after combination immune/targeted therapy and transarterial chemoembolization: two case reports and literature review

Xiao¹,

Zhang²,

Liang³

et al. 2022

Transl Cancer Res TCR

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Background: Effective treatment for patients with advanced unresectable hepatocellular carcinoma (HCC) is severely lacking. The most common clinical treatments include a combination of immunotherapy, molecular targeted agents, and transarterial chemoembolization (TACE). The combinations of therapies most likely to lead to complete recovery are unclear. The cases in this study were treated with TACE therapy and radiofrequency ablation followed by massive tumor antigen release as a way to enhance the effect of immune and targeted therapy, and TACE therapy followed by combination with programmed death 1 (PD-1) inhibitors and molecular targeted drugs may achieve better efficacy. We share two cases of advanced HCC patients who achieved complete response (CR) after treatment with PD-1 inhibitor combined with Lenvatinib and TACE and radiofrequency ablation to provide a reference for the treatment choice of advanced HCC patients.Case Description: We report two case studies of two Chinese men with advanced primary HCC (Barcelona Clinic Liver Cancer stage C) involving portal vein carcinoma thrombosis and Child-Pugh A liver function. Complete regression of the lesions and thrombosis was reached after TACE and radiofrequency ablation, followed by the combination of PD-1 inhibitor and Lenvatinib. Conclusions:We speculate that patients with advanced HCC with Child-Pugh A liver function may have better efficacy if they are treated with TACE and radiofrequency ablation followed by tumor necrosis and release of intratumoral antigens to achieve the effect of intensive immune and targeted therapy, and then sequential application of PD-1 inhibitors combined with molecular targeted drugs for conversion therapy. Further stimulate the body's immunity, so that the patient may reach CR. However, because surgical resection pathology was not performed, it is not clear whether pathological CR was achieved and the future prognosis remains to be further observed.

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Safety and Efficacy of Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Hepatocellular Carcinoma

Cited by 19 publications

References 35 publications

The Significance of Transarterial Chemo(Embolization) Combined With Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma in the Era of Systemic Therapy: A Systematic Review

The Significance of Transarterial Chemo(Embolization) Combined With Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma in the Era of Systemic Therapy: A Systematic Review

Four-Pyroptosis Gene-Based Nomogram as a Novel Strategy for Predicting the Effect of Immunotherapy in Hepatocellular Carcinoma

Complete response by patients with advanced hepatocellular carcinoma after combination immune/targeted therapy and transarterial chemoembolization: two case reports and literature review

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