Efficacy of Sorafenib Combined With Immunotherapy Following Transarterial Chemoembolization for Advanced Hepatocellular Carcinoma: A Propensity Score Analysis

Abstract

AimThe aim of the study is to compare the efficacy and safety of monotherapy with a sequential immune checkpoint inhibitor (ICI) programmed cell death protein-1 (PD-1) and its combination with multi-target drug sorafenib after transcatheter arterial chemoembolization (TACE) for advanced hepatocellular carcinoma (HCC).MethodsWe conducted a retrospective evaluation of patients with advanced HCC who had received sequential PD-1 sorafenib (duplex group, n = 25) or monotherapy PD-1 alone (PD-1 group, n = 41) after TACE during April 2018–September 2021. Propensity score matching (PSM) was applied to correct the selection bias, and 22 pairs were created. The objective response rate (ORR), duration of the overall response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events were analyzed for both groups.ResultsAfter PSM, the median PFS (7.63 vs. 2.9 months; p = 0.0335) was significantly longer for the duplex group than for the PD-1 group. The median OS (21.63 vs. 16.43 months; p = 0.103) was longer for the duplex group than for the PD-1 group, albeit without any statistical difference. The CR rate, ORR, DCR, and PFS rates at the first, third, and sixth months were higher for the duplex group than for the PD-1 group, wherein the PFS rate of the third and sixth months were statistically different. The OS rates at the sixth, 12th, and 18th months were better for the duplex group than for the PD-1 group, while the 18th-month OS rate (54.5% vs. 33.9%, p = 0.030) were statistically different between them. The most common adverse events after TACE included liver function injury, leukocytopenia, and thrombocytopenia, albeit without any statistical differences between the groups. Cox regression analysis showed that sorafenib combined immunotherapy after TACE and the achieving of CR or PR during the treatment were independent factors affecting PFS. Moreover, CNLC stage-IIIa, TACE frequency ≤2, and achievement of CR or PR were independent influencing factors of OS.ConclusionsSequential PD-1 combined with sorafenib therapy after TACE for advanced HCC treatment is safe and effective, especially for patients with good initial treatment response, to further improve the disease prognosis.

Lenvatinib plus transarterial chemoembolization with or without immune checkpoint inhibitors for unresectable hepatocellular carcinoma: A review

“…TACE only worked on intrahepatic lesions, and had no effect on extrahepatic metastasis; thus, combination with systemic therapy is necessary ( 61 ). In addition, TACE could lead to necrosis of tumor tissue and upregulate the expression of hypoxia-inducible factor 1-α (HIF-1α), vascular endothelial growth factor (VEGF), and fibroblast growth factor (FGF), which could stimulate tumor recurrence or growth ( 2 , 34 , 42 , 61 ). However, lenvatinib administration after TACE could suppress the effects of angiogenic factors ( 2 , 40 ).…”

Recent Progress in Advanced Hydrogel‐Based Embolic Agents: From Rational Design Strategies to Improved Endovascular Embolization

“…[219][220][221] In the clinic, TACE has been combined with immunotherapy to treat HCC, which improved the clinical outcome compared to TACE alone. [222][223][224] However, the systemic administration of immune checkpoint inhibitors (e.g., anti-PD-L1, anti-PD-1) causes substantial systemic adverse effects with compromised therapeutic effects, which undoubtedly limit their wide application in the clinic. [225,226] Hydrogels are favorable to be used as a drug depot to encapsulate immunotherapy drug and facilitate the local immunomodulation of the tumor microenvironment.…”

Transarterial chemoembolization plus apatinib with or without camrelizumab for unresected hepatocellular carcinoma: A two-center propensity score matching study

“…Several studies ( 13 , 14 ) have shown that TACE combined with anti-angiogenic therapy and immunotherapy can improve the treatment efficacy of patients with unresectable HCC, with an ORR of approximately 35%–59% and median overall survival (OS) of approximately 13–35 months. Few studies have been conducted using TACE along with apatinib and camrelizumab for patients with unresectable HCC.…”