Prognostic efficacy and prognostic factors of TACE plus TKI with ICIs for the treatment of unresectable hepatocellular carcinoma: A retrospective study

Abstract

Hepatocellular carcinoma (HCC) remains a global challenge due to its high morbidity and mortality rates as well as poor response to treatment. Local combined systemic therapy is widely used in the treatment of unresectable hepatocellular cancer (uHCC). This retrospective study was to investigate the prognostic effect and prognostic factors of transcatheter arterial chemoembolization (TACE) plus tyrosine kinase inhibitors (TKI) with immune checkpoint inhibitors (ICIs) in the treatment of uHCC. A retrospective analysis of 171 patients with uHCC was performed in our hospital from April 27, 2015 to October 18, 2021. According to different treatment options, patients were divided into TACE group (n=45), TACE+TKI group (n=76) and TACE+TKI+ICIs group (n=50). In this study, we found that, the median overall survival (mOS) of TACE+TKI+ICIs group was significantly better than TACE+TKI group and TACE group [24.1 (95% CI 15.1-33.1) months vs 14.9 (95% CI 10.7-19.1) months vs 11.4 (95% CI 8.4-14.5) months, hazard ratio (HR) 0.62; 95% CI 0.47-0.81; P=0.002]. A visible difference in the median progression-free survival (mPFS) interval between the groups was discovered [10.6 (95% CI6.5-14.7) months in TACE+TKI+ICIs group vs. 6.7 (95% CI 5.5-7.9) months in the TACE+TKI group vs. 6 (95% CI 2.3-9.7) months in the TACE group (HR 0.66; 95% CI 0.53-0.83; P<0.001)]. The objective response rates (ORR) in the TACE group, TACE+TKI group, and TACE+TKI+ICIs group were 31.1%, 35.5%, and 42%, and the disease control rate (DCR) were 51.1%, 65.8%, and 80%. There were no adverse events (AEs) of arthralgia, diarrhea, rash, and pruritus in the TACE group. The incidence of grade 3 AEs (Hypertension) in the TACE+TKI+ICIs group was significantly higher than that in TACE+TKI and TACE groups (28% vs 17.1% vs 6.7%, P=0.024), and secondly, the morbidity of rash and pruritus in the TACE+TKI+ICIs group was apparently higher than that in the TACE+TKI group (P<0.05). Multivariate analysis showed that ECOG-PS 2 (HR=2.064, 95%CI 1.335-3.191, P=0.001), Hepatitis B virus (HR=2.539, 95%CI 1.291-4.993, P=0.007), AFP≥400 ng/ml (HR= 1.72, 95%CI 1.12-2.643, P=0.013), neutrophil-lymphocyte ratio (NLR) ≥2.195 (HR=1.669, 95%CI 1.073-2.597, P=0.023) were independent risk factors for OS in uHCC patients. So, TACE+TKI+ICIs therapy can prolong the OS and improve the prognosis of patients effectively, with a well-characterized safety profile.

Comparable Clinical Outcomes Between Transarterial Chemoembolization or Hepatic Arterial Infusion Chemotherapy Combined with Tyrosine Kinase Inhibitors and PD-1 Inhibitors in Unresectable Hepatocellular Carcinoma

“…The reported mOS was 19.8 to 24.1 months for TTP and was 15.9 to not reached for HTP. [20][21][22][23] Consistent with our study, TACE-and HAIC-based combination therapies brought favorable and satisfying survival benefits in the treatment of advanced HCC, though significant differences in tumor response and survival outcomes between the two groups were not reached. However, the differences should not be ignored for they might be caused by the limited number of cases.…”

“…Han et al reported that TACE plus TKI and PD-1 inhibitors showed a mOS of 24.1 months, a mPFS of 10.6 months, ORRs of 42% and DCRs of 80%. 21 In addition, Guo et al demonstrated that the sequential combination of TACE with PD-1 inhibitors and TKIs for patients with advanced HCC significantly improved markers of treatment efficacy (mOS, 19.8 months; mPFS, 11.7 months; ORRs, 48.4%). 22 The combination therapies of HAIC, TKIs and PD-1 inhibitors have also been reported to have improved response rates and survival outcomes for unresectable HCC patients.…”

Research progress of targeted therapy combined with immunotherapy for hepatocellular carcinoma

“…This study is the first international multicenter phase III clinical study of anti-PD-1 monoclonal antibodies in combination with an anti-vascular targeted small molecule tyrosine kinase inhibitor on PFS and OS outcomes over sorafenib, and camrelizumab in combination with apatinib treatment achieved the longest OS benefit to date. In patients with HCC with a large tumor burden that cannot be resected, advanced hepatic artery chemoembolization combined with AC has better survival than early combination ( 55 , 56 ).…”

Safety and Efficacy of Transarterial Chemoembolization Combined with Tyrosine Kinase Inhibitor and Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma: A Single Center Experience

“…Furthermore, the ORR and DCR of triple therapy patients in Huang et al presented better outcomes than ICIs + TKI groups (12.5% and 50.0%), 32 42% and 80% in a study by Han et al presented better outcome thanTACE groups (31.1% and 51.1%) and TACE+TKI groups (35.5% and 65.8%), respectively. 33 These studies show that triple therapy has an advantage in terms of efficacy. Our results are comparable to those of other single-center investigative studies.…”