Hepatic arterial infusion chemotherapy combined with anti-PD-1/PD-L1 immunotherapy and molecularly targeted agents for advanced hepatocellular carcinoma: a real world study

Abstract

BackgroundMolecular targeted therapy combined with immunotherapy significantly improves the prognosis of patients with advanced liver cancer. Additionally, hepatic arterial infusion chemotherapy (HAIC) can improve the prognosis of patients with advanced liver cancer. This real-world study aimed to evaluate the clinical efficacy and safety of HAIC combined with molecular targeted therapy and immunotherapy in the treatment of primary unresectable hepatocellular carcinoma (uHCC).MethodsA total of 135 patients with uHCC were enrolled in this study. Progression-free survival (PFS) was the primary endpoint. The efficacy of the combination therapy was assessed based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines. Overall survival (OS), adverse events (AEs) and surgical conversion rate were the secondary endpoints. Univariate and multivariate Cox regression analyses were performed to examine independent prognostic factors. For sensitivity analysis, inverse probability weighting (IPW) was used to balance the influence of the tested confounding factors between groups to verify the robustness of conversion surgery for survival benefits. The E-values were estimated to assess robustness to unmeasured confounders.ResultsThe median number of therapies was three. Approximately 60% of the patients had portal vein tumour thrombosis (PVTT). The most common targeted drugs were lenvatinib and bevacizumab, whereas the most common immunotherapy drug was sintilimab. The overall objective response rate (ORR) was 54.1%, and the disease control rate (DCR) was 94.6%. A total of 97 (72%) patients experienced AEs of grades 3–4. Fatigue, pain and fever were the most common symptoms of grade 3-4 AEs. The median PFS was 28 months and 7 months in the successful and unsuccessful conversion groups, respectively. The median OS was 30 months and 15 months in the successful and unsuccessful conversion groups, respectively. Successful conversion surgery, sex, hapatic vein invasion, BCLC stage, baseline tumour size, AFP levels and maximum therapeutic response were independent prognostic factors for PFS. Successful conversion surgery, number of interventions, hapatic vein invasion and total bilirubin levels were independent prognostic factors for OS. After IPTW, no standardised differences exceeding 0.1 were found. IPW-adjusted Kaplan–Meier curves showed that successful conversion surgery was an independent prognostic factor for both PFS and OS. The E-values of successful conversion surgery were 7.57 and 6.53 for OS and PFS, respectively, which indicated a relatively robust impact of successful conversion surgery on the prognosis of patients.ConclusionPatients with primary uHCC undergoing HAIC combined with immunotherapy and molecular targeted therapy have a higher tumour regression rate and the side effects are manageable. Patients undergoing surgery after combination therapy have survival benefits.

Efficacy and safety of hepatic arterial infusion chemotherapy combined with lenvatinib and PD-1 inhibitors for advanced hepatocellular carcinoma with macrovascular invasion

“…In multivariate analysis, extrahepatic metastasis and Child-Pugh classification were independent prognostic factors for PFS. The results were worse than in previous studies [ 24 , 25 ]. The main reasons for the difference may be the following: the current study not only included HCC with PVTT, but also patients with hepatic vein and vena cava tumor thrombus, which accounted for 25%, and the average HAIC cycles received in this study was less than that of the studies before.…”

“…Another clinical trial that enrolled 247 HCC patients with portal vein invasion indicated that sorafenib plus HAIC has significantly longer OS when compared with sorafenib monotherapy (13.37 months vs. 7.13 months) [ 24 ]. More and more studies are trying to explore the safety and efficacy of the combination of HAIC, anti-PD-1/PD-L1 immunotherapy, and molecularly targeted agents and find the promising benefits of these combinations [ 25 , 26 ]. However, no study focuses on HCC patients with macrovascular invasion.…”

Neoadjuvant targeted immunotherapy followed by surgical resection versus upfront surgery for hepatocellular carcinoma with macrovascular invasion: A multicenter study

“…Compared to upfront surgery, patients receiving neoadjuvant targeted immunotherapy have a statistically significant increase in postoperative nononcologic mortality, but the difference is relatively small and may decrease with an increase in sample size. Numerous studies have shown that targeted immunotherapy is safe and well-tolerated 41 , 42 , and our two study groups did not have a significant difference in the occurrence of other major postoperative complications, indicating the safety of neoadjuvant targeted immunotherapy. Additionally, even though there is a slight increase in the risk of postoperative nononcologic mortality with neoadjuvant targeted immunotherapy, this risk is accidental and can be improved.…”

A preliminary study of optimal treatment response rates in patients undergoing hepatic arterial infusion chemotherapy combined with molecular targeting and immunotherapy

“…For antiangiogenic therapy, the patients were administered 8 mg of lenvatinib orally once daily, sorafenib 200 mg twice daily, and apatinib 250 mg once daily. Please refer to our previously published 001 Research for detailed treatment of patients ( 14 ).…”

“…Recent studies have shown that for primary unresectable HCC, HAIC treatment combined with targeted therapy and immunotherapy can achieve a significant surgical conversion rate ( 14 , 15 ). Although these findings are optimistic for individuals with unresectable HCC, it is important to note that not all patients may benefit from this combination therapy.…”