Effectiveness and safety of angiogenesis inhibitors combined with PD-1/PD-L1 blockades in the first-line treatment of patients with advanced hepatocellular carcinoma: A single-center retrospective study

Abstract

The combination of immune checkpoint inhibitors targeting anti-programmed cell death-1 (anti-PD-1) or anti-programmed death ligand-1 (anti-PD-L1) with antiangiogenic agents has emerged as a revolutionary therapy for advanced hepatocellular carcinoma (aHCC). Key antiangiogenic medications encompass monoclonal antibodies targeting vascular endothelial growth factor (anti-VEGF mAbs) and multiple kinase inhibitors (MKIs). The aim of this study is to assess the difference of efficacy and safety between 2 combination therapies. This study retrospectively examined the outcomes of 57 patients with aHCC who underwent first-line treatment with a combination of immune checkpoint inhibitors and antiangiogenic therapy at the First Affiliated Hospital of Anhui Medical University, from September 2018 to July 2023. The analysis, conducted using SPSS software, focused on patient outcomes such as tumor response (assessed according to modified Response Evaluation Criteria in Solid Tumors criteria), objective response rate, disease control rate, progression-free survival, overall survival, and safety. Comparisons among different groups were also made. The anti-PD-1/anti-PD-L1-anti-VEGF mAbs group showed a trend of higher partial response rate (37.50% vs 22.45%), objective response rate (37.50% vs 24.49%), disease control rate (62.50% vs 59.18%), and seemed to achieve longer median progression-free survival (14.93 vs 14.90 months) and median overall survival (15.80 vs 11.10 months) without higher grade 3 or higher adverse events comparing to anti-PD-1/anti-PD-L1-MKIs group. Subgroup analysis showed that the anti-PD-1-lenvatinib group achieved longer median progression-free survival (23.97 months), while the anti-PD-1-regorafenib group achieved longer median overall survival (37.97 months). The anti-PD-1/anti-PD-L1 combined with anti-VEGF mAbs was effective and tolerable compared to anti-PD-1/anti-PD-L1-MKIs in aHCC. The addition of lenvatinib or regorafenib may provide promising incremental benefit for patients with aHCC.

Figure 1.

Kaplan–Meier curves according to therapeutic regimens. (A) PFS according to therapeutic regimens (anti-PD-1/anti-PD-L1 and anti-VEGF mAbs combination therapy vs anti-PD-1/anti-PD-L1 and MKIs combination therapy). (B) OS according to therapeutic regimens (anti-PD-1/anti-PD-L1 and anti-VEGF mAbs combination therapy vs anti-PD-1/anti-PD-L1 and MKIs combination therapy). Anti-PD-1 = anti-programmed cell death-1, anti-PD-L1 = anti-programmed death ligand-1, anti-VEGF mAbs = monoclonal antibodies targeting vascular endothelial growth factor, MKIs = multiple kinase inhibitors, OS = overall survival, PFS = progression-free survival.

Figure 2.

Kaplan–Meier curves according to therapeutic regimens. (a) PFS according to therapeutic regimens (anti-PD-1 and anti-VEGF mAbs combination therapy vs anti-PD-1 and MKIs combination therapy). (b) OS according to therapeutic regimens (anti-PD-1 and anti-VEGF mAbs combination therapy vs anti-PD-1 and MKIs combination therapy). Anti-PD-1 = anti-programmed cell death-1, anti-PD-L1 = anti-programmed death ligand-1, anti-VEGF mAbs = monoclonal antibodies targeting vascular endothelial growth factor, MKIs = multiple kinase inhibitors, OS = overall survival, PFS = progression-free survival.