Hepatic arterial infusion chemotherapy combined with PD-1 inhibitors and tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: A tertiary medical center experience
Laihui Luo, Yongqiang Xiao, Guoqing Zhu, Aihong Huang, Shengjiang Song, Tao Wang, Xian Ge, Jin Xie, Wei Deng, Zhigao Hu, Wu Wen, Haoran Mei, Renhua Wan, Renfeng Shan
Abstract
Background Unresectable hepatocellular carcinoma (u-HCC) still accounts for the majority of newly diagnosed HCC which with poor prognosis. In the era of systemic therapy, combination therapy with programmed cell death protein-1 (PD-1) inhibitors and tyrosine kinase inhibitors (TKIs) has become mainstream. Hepatic arterial infusion chemotherapy (HAIC) as a local treatment has also shown a strong anti-tumor effect. This study aimed to investigate the efficacy and safety of HAIC, PD-1 inhibitors plus TKIs for u-HCC. Methods This retrospective study included patients with initially u-HCC between October 2020 to April 2022 who had received at least one cycle of therapy with HAIC, PD-1 inhibitors plus TKIs. The primary outcome included overall response rate (ORR), the disease control rate (DCR), surgical conversion rate, progression-free survival (PFS) and treatment-related adverse events. Results A total of 145 patients were included in the study. The median treatment cycle of HAIC and PD-1 inhibitors were 3 and 4, respectively. According to the modified RECIST criteria, the best ORR was 57.2% (83/145), 9 had achieved complete response (CR), DCR was 89.7% (130/145). Median time to achieve CR or PR was 65 days. Surgical conversion rate was 18.6% (27/145), seven patients (7/27,25.9%) achieved pathological complete response (pCR). The median follow-up was 12.5 months (4.5-20 months), and the median PFS was 9.7 months. Subgroup analysis showed that Child-pugh A patients had higher DCR (92.2% vs 79.3%, p =0.041) than Child-pugh B patients, as well as increased successful conversion rate (22.4% vs 3.4%, p =0.019). Patients without vascular invasion and extrahepatic metastases showed higher PR (63.4% vs 43.3%, p <0.05) and ORR (73.2% vs 50.0%, p <0.05) than those with vascular invasion. The ORR (73.2% vs 45.5%, p <0.05) and DCR (95.1% vs 78.8%, p <0.05) were also significantly better than those of patients with extrahepatic metastases. HAIC regimen was not related to efficacy (All p >0.05). The incidence rate of grade 3/4 treatment-related AEs was 17.7% without fatal events. Conclusion The triple combination therapy of HAIC and PD-1 inhibitors plus TKIs for patients with initially unresectable HCC exhibited satisfactory efficacy with tolerable toxicity.