Tyrosine Kinase Inhibitors Plus Anti-PD-1 Antibodies with Hepatic Arterial Infusion Chemotherapy or Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma

Bingran Yu; Ning Zhang; Yun Feng; Yongfa Zhang; Ti Zhang; Lu Wang

doi:10.2147/JHC.S431917

Tyrosine Kinase Inhibitors Plus Anti-PD-1 Antibodies with Hepatic Arterial Infusion Chemotherapy or Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma

J Hepatocell Carcinoma. 2023 Oct 6:10:1735-1748. doi: 10.2147/JHC.S431917. eCollection 2023.

Authors

Bingran Yu¹, Ning Zhang¹, Yun Feng¹, Yongfa Zhang¹, Ti Zhang¹, Lu Wang¹

Affiliation

¹ Department of Hepatic Surgery, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.

Abstract

Background: The combination of tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies with hepatic arterial infusion chemotherapy (HAIC) or transarterial chemoembolization (TACE) has shown encouraging anti-tumor effects in the treatment of hepatocellular carcinoma (HCC). We explored the efficacy and safety of TKIs and anti-PD-1 antibodies combined with HAIC or TACE in HCC.

Methods: Data from 302 HCC patients receiving HAIC combined with TKIs and anti-PD-1 antibodies (HAIC-TP group) and 446 HCC patients receiving TACE combined with TKIs and anti-PD-1 antibodies (TACE-TP group) were retrospectively collected. Clinicopathological characteristics, tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were compared between two groups. Propensity score matching (PSM) analysis was performed to minimize bias.

Results: The HAIC-TP group exhibited better objective response rate (RECIST: 33.1% versus 7.8%, P < 0.001; mRECIST: 51.4% versus 17.5%, P < 0.001), longer PFS (12.4 months versus 8.2 months, P < 0.001), and longer OS (not reached versus 13.8 months, P < 0.001) than TACE-TP group. Surgery was performed after combination therapy in 34 patients of the HAIC-TP group and in 7 patients of the TACE-TP group (P < 0.001). Similar results were also observed in the PSM analysis. Multivariate analysis indicated type of treatment, alpha-fetoprotein, ALBI grade, portal vein tumor thrombus, and extrahepatic status were risk factors for poor prognosis. Nausea, vomiting, diarrhea, and abdominal pain occurred more frequently in the HAIC-TP group, whereas liver dysfunction occurred more frequently in the TACE-TP group. All AEs were acceptable and manageable as a result of treatment interruption or dose modification.

Conclusion: The combination of HAIC with TKIs and anti-PD-1 antibodies is an effective and safe therapeutic regimen over TACE-based combination therapy for patients with HCC. A prospective study with a large sample size is required to validate the efficacy and safety of the combination therapy.

Keywords: combination therapy; hepatic arterial infusion chemotherapy; hepatocellular carcinoma; transarterial chemoembolization.

Grants and funding

This work was jointly supported by the National Natural Science Foundation of China (81874182), National Science and Technology Major Project (2018ZX10723204-007-004), Shanghai Municipal Health Bureau (201940043), and the Shanghai Hospital Development Center (SHDC12019X19).