Interaction between hepatitis B virus infection and the efficacy of camrelizumab in combination with apatinib therapy in patients with hepatocellular carcinoma: a multicenter retrospective cohort study

Abstract

Background: The interaction between hepatitis B virus (HBV) load and anti-programmed cell death (PD)-1 in combination with (+) antiangiogenic therapy remains controversial, especially for hepatocellular carcinoma (HCC) patients. This study sought to explore the effects of HBV load and antiviral therapy on anti-PD-1+ antiangiogenic therapy, and the rate of HBV reactivation during anti-PD-1+ antiangiogenic treatment.Methods: We performed a multicenter retrospective cohort study of camrelizumab combined with apatinib (C+A) therapy between January 1, 2019 and January 1, 2021 in patients with unresectable HCC who were seropositive for hepatitis B surface antigen (HBsAg) and received antiviral therapy before C+A involvement.The effects of HBV load and antiviral therapy on C+A and the rate of HBV reactivation during C+A treatment were examined.Results: Eighty-six patients were included in the analysis. The patients had a mean age of 55 years, and 72 (83.7%) were male. The objective response rates (ORRs) in patients with low (<2,000 IU/mL) and high (≥2,000 IU/mL) baseline HBV deoxyribonucleic acid (DNA) levels were 34.5% and 32.2%, respectively (χ²=0.046; P=0.829), while the disease control rates (DCRs) were 67.3% and 80.6%, respectively (χ²=1.762; P=0.184). The results of the univariate and multivariate analyses showed that the baseline HBV DNA level did not affect PD. Additionally, none of the 86 patients suffered from HBV reactivation or HBV-related hepatic impairment with continuous antiviral treatment, regardless of nucleos(t)ide analogue (NA) type (F=1.473; P=0.228).Conclusions: Baseline HBV loads did not affect the tumor responses of HCC patients receiving anti-PD-1+ antiangiogenic therapy. Thus, HBV reactivation should not be a contradiction for anti-PD-1+ antiangiogenic therapy among patients undergoing continuous and effective antiviral treatment.

Correlation of HBV DNA and Hepatitis B Surface Antigen Levels With Tumor Response, Liver Function and Immunological Indicators in Liver Cancer Patients With HBV Infection Undergoing PD-1 Inhibition Combinational Therapy

“…HBV DNA is often associated with poor prognosis in the local or systemic treatment of liver cancer ( 21 – 28 ). However, during PD-1/PD-L1 ICI treatment, patients with HBV-related liver cancer had a similar tumor response to that of all patients.…”

“…In most clinical trials for PD-1/PD-L1 ICIs, liver cancer patients with HBV infection were required to have a baseline HBV load <100 IU/mL for eligibility; therefore, the effect of baseline viral load on clinical outcomes could not be assessed. However, several studies have enrolled patients with a high viral load, suggesting an absence of correlation between baseline HBV viral load and patient OS and PFS during PD-1/PD-L1 treatment; however, the presence or absence of antiviral therapy during immunotherapy could affect tumor prognosis ( 27 , 28 ).…”

Research progress of targeted therapy combined with immunotherapy for hepatocellular carcinoma

“…Target-immunity combination therapy as a neoadjuvant option for resectable HCC can reduce the 1-year postoperative recurrence rate and improve the 1-year survival rate without compromising the safety of surgery ( 45 ). In addition, several studies have shown that HBV load does not affect tumor response in HCC patients treated with camrelizumab in combination with apatinib ( 46 ). The combination of camrelizumab and apatinib for advanced HCC with portal vein tumor thrombosis has good efficacy and controllable side effects, and is worth promoting in the clinic ( 47 ).…”

Comparison of effectiveness and safety of camrelizumab between HBV-related and non-B, non-C hepatocellular carcinoma: A retrospective study in China

“…Sun et al (2020) found no significant correlation between clinical outcomes and HBV loads in HCC patients receiving the PD-1 inhibitor. In addition, Yuan et al (2021) found that HBV loads did not affect the short-term efficacy of the PD-1 inhibitor combined with antiangiogenic therapy for HCC patients. NAFLD refers to a clinical syndrome characterized by excessive deposition of fat in liver cells, apart from alcohol and other definite liver damage factors (Eslam et al, 2020).…”