Efficacy and Safety of Hepatic Arterial Infusion Chemotherapy(HAIC) Combined with PD-1 Inhibitors for Advanced Hepatocellular Carcinoma with Macrovascular Invasion: A Multicenter Propensity Score Matching Analysis

Fengtao Zhang,1,&ast; Sheng Zhong,2,&ast; Qiming Wei,3 Haiming Zhang,4 Honglei Hu,5 Bicheng Zeng,6 Xiang Zheng7 1Vascular Interventional Surgery, Huazhong University of Science and Technology Union Shenzhen Hospital(Shenzhen Nanshan People’s Hospital), Shenzhen, Guangdong, 518000, People’s Republic of China; 2Department of Tumor and Vascellum Intervention, DongGuan Tungwah Hospital, DongGuan, Guangdong, 523000, People’s Republic of China; 3Department of Interventional Therapy, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510000, People’s Republic of China; 4Department of Radiology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510080, People’s Republic of China; 5Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510260, People’s Republic of China; 6Hepatobiliary Surgery, The Sixth Affiliated Hospital of Jinan University, Dongguan, Guangdong, 523000, People’s Republic of China; 7Department of Interventional Therapy, Zhuhai People’s Hospital(Zhuhai Clinical Medical College of Jinan University), Zhuhai, Guangdong, 519000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Zheng, Department of Interventional Therapy,Zhuhai People’s Hospital(Zhuhai Clinical Medical College of Jinan University), No. 79 Kangning Road, Zhuhai, 519000, People’s Republic of China, Email [email protected]: To investigate the efficacy and safety of HAIC combined with programmed cell death protein-1 (PD1) inhibitors in MVI-positive advanced hepatocellular carcinoma(HCC).Methods: From September 2017 to May 2019, we retrospectively collected the clinical data from three medical centers in China pertaining to patients diagnosed with BCLC C stage HCC with MVI and receiving treatment with a combination of HAIC and PD-1 inhibitors treatment or HAIC alone, and we compared the efficacy of HAIC combined with PD-1 inhibitors and HAIC monotherapy. Propensity score matching(PSM) was utilized to adjust for baseline differences between groups. Survival outcomes and tumor response rate were used to assess survival benefits, while the incidence of adverse events was used to evaluate safety.Results: After screening for eligibility, 489 patients diagnosed with HCC and concomitant MVI were enrolled. Of these, 173 patients received treatment combining HAIC with PD-1 inhibitors, while 316 patients underwent HAIC monotherapy. After PSM adjustment, the combination therapy group demonstrate superior survival outcomes. Median overall survival(OS) and progression free survival(PFS) were 31.8 months and 10.8 months, respectively, significantly higher than those in the monotherapy group (OS: 10.0 months; PFS: 6.1 months; both P< 0.0001). Moreover, ORR and DCR remained significantly elevated in the combination therapy group (ORR: 44.3% vs 20.4%, P< 0.0001; DCR: 89.8% vs 82.0%, P=0.041). Safety profiles indicated no significant differences in adverse event rates between the two treatment groups, encompassing both overall and grade-specific assessments.Conclusion: Compared to HAIC alone, the combination of HAIC with PD-1 inhibitors represents a more promising and effective approach for patients with HCC complicated by macrovascular invasion.Keywords: hepatocellular carcinoma, programmed cell death protein 1, hepatic artery infusion chemotherapy, macrovascular invasion, propensity score matching