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. 2022 May 23:13:913464.
doi: 10.3389/fimmu.2022.913464. eCollection 2022.

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

Qiao Ke  1   2 , Fuli Xin  1   2 , Huipeng Fang  2 , Yongyi Zeng  1 , Lei Wang  2   3 , Jingfeng Liu  4   5
Affiliations

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

Qiao Ke et al. Front Immunol. .

Erratum in

Abstract

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.

Keywords: hepatic arterial infusion chemotherapy; hepatocellular carcinoma; immune checkpoint inhibitors; systematic review; transarterial chemotherapy; tyrosine kinase inhibitors.

PubMed Disclaimer

Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Flow diagram for study selection.
Figure 2
Figure 2
Forest plot of the pooled complete response.
Figure 3
Figure 3
Forest plot of the pooled objective response rate.
Figure 4
Figure 4
Forest plot of the pooled disease control rate.
Figure 5
Figure 5
Forest plot of the pooled surgical conversion rate.
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