Correlation and efficacy of TACE combined with lenvatinib plus PD‐1 inhibitor in the treatment of hepatocellular carcinoma with portal vein tumor thrombus based on immunological features

Abstract

Background Although the appearance of portal vein tumor thrombus (PVTT) is significantly associated with unfavorable prognosis, there is insufficient evidence to confirm the efficacy and safety of the triple combination of transarterial chemoembolization (TACE), lenvatinib, and programmed cell death‐1 (PD‐1) inhibitor for patients with hepatocellular carcinoma (HCC) and PVTT. Furthermore, it remains unclear which patient type can obtain the best survival benefit from this combination therapy. Methods The data of 160 patients with HCC and PVTT treated with TACE combined with lenvatinib plus PD‐1 inhibitor (TACE+LEN + PD‐1 group) or TACE combined with lenvatinib (TACE+LEN group) were retrospectively collected and analyzed. To estimate the efficacy and safety of combination therapy for patients with advanced HCC, tumor response, progression‐free survival (PFS), overall survival (OS), biochemical indices, and adverse events (AEs) were assessed in this study. More importantly, tumor immune‐related cytokines were used to identify biomarkers predicting the therapeutic response of combination therapy. Results TACE+LEN + PD‐1 was superior to TACE+LEN in OS (23.5 vs. 18.3 months, p = 0.0002) and PFS (7.5 vs. 4.3 months, p < 0.0001). Moreover, TACE+LEN + PD‐1 achieved more preferable benefits with respect to disease control rate (80.00% vs. 56.67%) and objective response rate (38.57% vs. 24.45%) compared with TACE+LEN in patients with HCC and PVTT (p = 0.025). Multivariate analysis showed that Child–Pugh grade, PVTT classification, treatment option, and interleukin (IL)‐6, IL‐17, interferon (IFN)‐α, and vascular endothelial growth factor (VEGF) levels were independent factors related to OS, whereas PVTT classification, treatment option, and IL‐6 and IFN‐α levels were independent factors related to PFS. Furthermore, the subgroup analysis illustrated that the inflammatory cytokines VEGF, IL‐6, IL‐17, and IFN‐α might be novel biomarkers for predicting the survival prognosis of patients with advanced HCC and PVTT treated with TACE+LEN + PD‐1. The safety in the combination group was acceptable. Conclusions Compared with TACE+LEN, the triple combination treatment of TACE+LEN + PD‐1 has more promising clinical outcomes and acceptable safety in patients with HCC and PVTT. Child–Pugh grade, PVTT classification, and IL‐6, IL‐17, IFN‐α, and VEGF levels are independent prognostic factors for survival time.

Efficacy and safety of TACE combined with tyrosine kinase inhibitors and camrelizumab for unresectable hepatocellular carcinoma: A systematic review and meta‑analysis

“…The results suggested that T-T-C combination therapy resulted in an improved OS, PFS, ORR and DCR compared with T-T combination therapy. A study by Zou et al ( 52 ) included 160 patients with advanced liver cancer, all receiving TACE + lenvatinib with or without PD-1 inhibitors, and focused on patient outcomes. The results showed that the triple therapy significantly extended the median OS (23.5 vs. 18.3 months; P=0.0002) and PFS (7.5 vs. 4.3 months; P<0.0001) times compared with the double therapy.…”

Pretreatment CT-based machine learning radiomics model predicts response in unresectable hepatocellular carcinoma treated with lenvatinib plus PD-1 inhibitors and interventional therapy

“… 35 Furthermore, serum procalcitonin levels and inflammatory cytokines VEGF, interleukin (IL)-17, IL-6, and IFN-α were found to be predictive biomarkers for lenvatinib in combination with TACE and PD-1 inhibitors in advanced HCC with large-vessel invasion. 36 37 However, the clinical application of the above-reported biomarkers was limited by the biological samples collection, low cost-effectiveness, and the prediction accuracy remained to be further improved. Moreover, relative studies have shown that radiomics can serve as a non-invasive and easily available method to predict treatment response in the past decade.…”

Case report: Complete response after transcatheter arterial chemoembolization combined with donafenib plus tislelizumab therapy for hepatocellular carcinoma with main trunk portal vein tumor thrombus in a patient coinfected with HIV and HBV

“…Moreover, Zou et al. illustrated that TACE combined lenvatinib and PD-1 inhibitors has more promising clinical outcomes and acceptable safety when compared with TACE plus lenvatinib in patients with HCC and PVTT ( 21 ).…”