A Combination of Sorafenib, an Immune Checkpoint Inhibitor, TACE and Stereotactic Body Radiation Therapy versus Sorafenib and TACE in Advanced Hepatocellular Carcinoma Accompanied by Portal Vein Tumor Thrombus

Abstract

Background: This study compared the effectiveness of the combined administration of sorafenib, an immune checkpoint inhibitor, transcatheter arterial chemoembolization (TACE), and stereotactic body radiation therapy (SBRT) (SITS group) vs. sorafenib combined with TACE (ST group) in treating and downstaging advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Methods: The present study included patients with advanced HCC and PVTT treated with one of the above combination therapies. The downstaging rate, objective response rate (ORR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs) were assessed. Results: Sixty-two patients were analyzed. The ORR was elevated in the SITS group compared with the ST group (p = 0.036), but no differences were found in DCR (p = 0.067). The survival analysis revealed higher PFS (p = 0.015) and OS (p = 0.013) in the SITS group, with median PFS and OS times of 10.4 and 13.8 months, respectively. Ten patients displayed successful downstaging and underwent surgery in the SITS group, vs. none in the ST group. The prognosis was better in surgically treated patients compared with the non-surgery subgroup, based on PFS (p < 0.001) and OS (p = 0.003). Despite a markedly higher rate of AEs in the SITS group (p = 0.020), including two severe AEs, the SITS combination therapy had an acceptable safety profile. Conclusion: The SITS combination therapy yields higher PFS and OS than the combined administration of sorafenib and TACE in patients with advanced HCC and PVTT, especially as a downstaging strategy before surgery.

Efficacy and safety of PD1/PDL1 inhibitors combined with radiotherapy and anti-angiogenic therapy for solid tumors: A systematic review and meta-analysis

“…Three nonrandom comparative studies [18,19,21] have reported the ORR and DCR. The pooled ORR and pooled DCR were HR = 1.519 (95% CI: 1.052–2.194, P = .026) and HR = 1.194 (95% CI: 1.074–1.327), respectively (Fig.…”

“…AEs were reported in all the included studies. Three studies [20][21][22] reported any-grade AEs and 8 studies [13][14][15][16][17][18]20,21] reported grade 3 to 4 AEs. The pooled rate of any-grade AEs was 86% (95% CI: 77-93%, P = .00).…”

“…This study included subgroup analyses. Among the different therapeutic regimens, RIT plus chemotherapy (RITC) therapy was administered in 2 studies, [13,21] and the pooled ORR and DCR were 50% (95% CI: .079 0.00, .396 [13,18,21] Skin reaction 14 9-19 .00 0.00, .5 [13,14,[16][17][18]20,21] Aspartate aminotransferase increased 18 13-25 .00 0.00, .98 [17][18][19][20] Alanine aminotransferase increased 22 14-31 .00 0.00, .91 [17,18,20] Anemia 20-80%, P = .001) and 69% (95% CI: 39-99%), respectively, while the pooled ORR and DCR were 61% (95% CI: 49-73%, P = .00) and 95% (95% CI: 83-107%) in the RIT therapy group. ORR in the RIT group was pooled using a random-effect model because of slight heterogeneity (I 2 = 47.6%, P = .075) (Figs.…”

“…Six studies [14,15,17,[19][20][21] reported CRR. The pooled CRR was 48% (95% CI: 35-61%, P = .00), but there was significant heterogeneity among the 6 trials mentioned (I 2 = 83.7%, P = .00) (Fig.…”

Transarterial chemoembolization combined with lenvatinib, programmed death-1 inhibitor, and iodine-125 seed brachytherapy for hepatocellular carcinoma with portal vein tumor thrombosis

“…Therefore, the combination therapy comprising lenvatinib, TACE, PD-1 inhibitor, and I 125 seed brachytherapy is expected to have a better therapeutic effect in the treatment of HCC, especially in patients with PVTT. Two preclinical studies supported the quadruple therapy, for example, Huang Y et al 18 demonstrated that combination therapy of TACE, stereotactic Body Radiation Therapy (SBRT), sorafenib, and camrelizumab had a survival bene t, extending the PFS to 15.7 months for HCC patients with PVTT; Zhang et al 45 reported that the combination of sorafenib, an immune checkpoint inhibitor, TACE, and SBRT have a median OS of 24.2 months and PFS of 24.2 months 45 . However, our study reported a lower OS of 21.0 months and a PFS of 13.0 months.…”