The Efficacy and Safety of Bevacizumab Plus Anti-PD-1/PD-L1 Inhibitors in Combination with Hepatic Arterial Infusion Chemotherapy for Initially Unresectable Hepatocellular Carcinoma

Xiang Tang,1,2,* Jinbin Chen,1,2,* Wei Peng,1,2,* Zhoutian Yang,1,2 Li Hu,1,2 Zhiwei Ye,1,2 Yizhen Fu,1,2 Dandan Hu,1,2 Zhongguo Zhou,1,2 Minshan Chen,1,2 Yaojun Zhang,1,2 Jun-Cheng Wang1,2 1State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yaojun Zhang; Jun-Cheng Wang, Department of Liver Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of China, Email [email protected]; [email protected]: To report the efficacy and safety of triple combination therapy with bevacizumab plus anti-PD-1 (BP1) or anti-PD-L1 inhibitors (BPL) combined with hepatic arterial infusion chemotherapy (HAIC) as a first-line treatment for initially unresectable hepatocellular carcinoma (uHCC).Methods: In this retrospective study, patients with initially uHCC received either BP1-HAIC or BPL-HAIC as first-line treatment. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR).Results: Between January 2020 and December 2022, a total of 136 patients with initially uHCC received triple combination therapy, with 76 in the BP1-HAIC group and 60 in the BPL-HAIC group. The median PFS for the entire cohort was 11.1 months (95% CI, 8.0– 13.7 months), and the median OS was 22.4 months (95% CI, 21.3- not reached). Comparative analysis revealed no significant differences in PFS (HR, 0.91, P = 0.69) or OS (HR, 0.71, P = 0.31) between the BP1-HAIC and BPL-HAIC groups. The ORR was 46.3% per RECIST v1.1 and 66.9% per mRECIST, with a DCR of 83.1% under both criteria. Common adverse events (AEs) included hypoalbuminemia and elevated aspartate/alanine aminotransferase, with 5.1% (7/136) experienced upper gastrointestinal bleeding. Multivariate Cox analysis identified tumor number and BCLC stage as independent prognostic factors for OS, and tumor number for PFS.Conclusion: Triple combination therapy demonstrated significant therapeutic efficacy and tumor response in initially uHCC. No notable differences in outcomes were observed between the BP1-HAIC and BPL-HAIC groups. AEs were manageable in clinical practice.Keywords: hepatocellular carcinoma, immune checkpoint inhibitor, bevacizumab, hepatic arterial infusion chemotherapy, adverse event