PMID- 35677059 OWN - NLM STAT- MEDLINE DCOM- 20220610 LR - 20220719 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - 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. PG - 913464 LID - 10.3389/fimmu.2022.913464 [doi] LID - 913464 AB - BACKGROUND AND AIMS: Regardless 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. METHODS: PubMed, 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). RESULTS: A 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). CONCLUSION: With 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 REGISTRATION: http://www.crd.york.ac.uk/PROSPERO/, Review registry: CRD42022321970. CI - Copyright (c) 2022 Ke, Xin, Fang, Zeng, Wang and Liu. FAU - Ke, Qiao AU - Ke Q AD - Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China. AD - College of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou, China. FAU - Xin, Fuli AU - Xin F AD - Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China. AD - College of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou, China. FAU - Fang, Huipeng AU - Fang H AD - College of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou, China. FAU - Zeng, Yongyi AU - Zeng Y AD - Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China. FAU - Wang, Lei AU - Wang L AD - College of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou, China. AD - Department of Radiation Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China. FAU - Liu, Jingfeng AU - Liu J AD - Department of Hepatopancreatobiliary Surgery, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China. AD - The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China. LA - eng PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20220523 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Immune Checkpoint Inhibitors) RN - 0 (Protein Kinase Inhibitors) SB - IM EIN - Front Immunol. 2022 Jun 07;13:952446. PMID: 35747141 MH - *Carcinoma, Hepatocellular/pathology MH - *Chemoembolization, Therapeutic/methods MH - Humans MH - Immune Checkpoint Inhibitors/adverse effects MH - *Liver Neoplasms/drug therapy/pathology MH - Protein Kinase Inhibitors/adverse effects PMC - PMC9167927 OTO - NOTNLM OT - hepatic arterial infusion chemotherapy OT - hepatocellular carcinoma OT - immune checkpoint inhibitors OT - systematic review OT - transarterial chemotherapy OT - tyrosine kinase inhibitors COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/06/10 06:00 MHDA- 2022/06/11 06:00 PMCR- 2022/01/01 CRDT- 2022/06/09 02:06 PHST- 2022/04/05 00:00 [received] PHST- 2022/04/26 00:00 [accepted] PHST- 2022/06/09 02:06 [entrez] PHST- 2022/06/10 06:00 [pubmed] PHST- 2022/06/11 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.913464 [doi] PST - epublish SO - Front Immunol. 2022 May 23;13:913464. doi: 10.3389/fimmu.2022.913464. eCollection 2022.