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
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 tyrosi...
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Frontiers Media S.A.
2022-05-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.913464/full |
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| author | Qiao Ke Qiao Ke Fuli Xin Fuli Xin Huipeng Fang Yongyi Zeng Lei Wang Lei Wang Jingfeng Liu Jingfeng Liu |
| author_facet | Qiao Ke Qiao Ke Fuli Xin Fuli Xin Huipeng Fang Yongyi Zeng Lei Wang Lei Wang Jingfeng Liu Jingfeng Liu |
| author_sort | Qiao Ke |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T22:34:37Z |
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| last_indexed | 2024-12-11T22:34:37Z |
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| spelling | doaj.art-4ace2e73bc234c3198143731fff03d552022-12-22T00:48:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-05-011310.3389/fimmu.2022.913464913464The 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 ReviewQiao Ke0Qiao Ke1Fuli Xin2Fuli Xin3Huipeng Fang4Yongyi Zeng5Lei Wang6Lei Wang7Jingfeng Liu8Jingfeng Liu9Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, ChinaCollege of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou, ChinaDepartment of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, ChinaCollege of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou, ChinaCollege of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou, ChinaDepartment of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, ChinaCollege of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou, ChinaDepartment of Radiation Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, ChinaDepartment of Hepatopancreatobiliary Surgery, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, ChinaBackground 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.913464/fullhepatocellular carcinomatransarterial chemotherapyhepatic arterial infusion chemotherapytyrosine kinase inhibitorsimmune checkpoint inhibitorssystematic review |
| spellingShingle | Qiao Ke Qiao Ke Fuli Xin Fuli Xin Huipeng Fang Yongyi Zeng Lei Wang Lei Wang Jingfeng Liu Jingfeng Liu 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 Frontiers in Immunology hepatocellular carcinoma transarterial chemotherapy hepatic arterial infusion chemotherapy tyrosine kinase inhibitors immune checkpoint inhibitors systematic review |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | hepatocellular carcinoma transarterial chemotherapy hepatic arterial infusion chemotherapy tyrosine kinase inhibitors immune checkpoint inhibitors systematic review |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.913464/full |
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