952P - Comprehensive analysis of cytokines and PDL1 before and after administration of atezolizumab and bevasizumab in patients with HCC

Background

The atezolizumab/bevacizumab (ATZ/BV) combination therapy is the standard regimen for hepatocellular carcinoma. However, predictive biomarkers of treatment response are unknown. In this study, a prospective, single-arm, multicentre study was conducted to explore biomarkers associated with treatment response in ATZ/BV combination therapy for hepatocellular carcinoma.

Methods

Patients were enrolled between September 1^st, 2021 and March 31th, 2023 at nine cancer institutions in Japan. Inclusion criteria were: age ≥20 years, unresectable hepatocellular carcinoma, Child-Pugh class A, and no prior drug therapy for hepatocellular carcinoma. The target number of patients was set at 20, with 71 serum cytokine biomarker analyses performed before, after two courses and after four courses of ATZ/BV combination therapy, to analyze the association with recurrence.

Results

Of the 20 enrolled patients, one patient declined consent prior to administration of ATZ/BV combination therapy, so analyses were conducted in 19 patients. Patients were 15 men and 4 women with a median age of 73 years. The completion status of the four courses of ATZ/BV combination therapy was: 12 patients completed the course, four patients discontinued due to progressive disease, two patients discontinued due to side effects (liver failure) and one patient discontinued due to conversion to surgery after three courses. At one year, the response rate for the 19 patients was 2 partial remission, 2 stable disease and 15 progressive diseases. There were no immune-related side effects during the course of the study. One-year overall survival was 73.0% and one-year progression free survival (PFS) was 16.7% (median 8.2 months). Univariate analysis of serum cytokine biomarkers using the COX proportional hazards model showed that CCL26, CXCL1, CCL1, IFNγ, IL-10, IL-1β, CCL13, CCL25, TNFα and TRAIL were significantly associated with PFS.

Conclusions

Candidate biomarkers associated with treatment response in ATZ/BV combination therapy for hepatocellular carcinoma were identified; IFNγ and TRAIL are cytokines with potential for therapeutic intervention and may be expected to have an add-on effect to ATZ/BV combination therapy.

Clinical trial identification

UMIN000045131.

Editorial acknowledgement

Legal entity responsible for the study

National Center for Global Health and Medicine.

Funding

National Center for Global Health and Medicine.

Disclosure

All authors have declared no conflicts of interest.