Tislelizumab plus anlotinib with or without radiotherapy as first-line therapy in advanced hepatocellular carcinoma: a single center, non-randomized retrospective case–control study

The purpose of this study was to investigate the efficacy and safety of tislelizumab (monoclonal antibody) plus anlotinib (tyrosine kinase inhibitor) with or without radiotherapy in advanced hepatocellular carcinoma (HCC). Ninety patients with advanced HCC were divided into two groups: tislelizumab plus anlotinib with radiotherapy (TAR group) and tislelizumab plus anlotinib (TA group) based on the treatment received. Radiotherapy was performed on two or three days during the first cycle of tislelizumab plus anlotinib. The radiotherapy requirements were dose_95% ≥ 14.2-46 Gy for tumor volume. Efficacy was evaluated according to the modified Response Evaluation Criteria for Solid Tumors. Adverse events (AEs) were evaluated using the National Cancer Institute-Common Terminology Criteria for Adverse Events 4.0. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and the disease control rate (DCR). The ORR and DCR in the TAR group were 24.5% (62.2% and 37.7%, p = 0.03) and 22.3% higher (75.6% and 53.3%, p = 0.04), respectively, compared to the TA group. The median OS and PFS in the TAR group were prolonged 4.5 months [21.0 and 16.5 months, χ² = 8.99, p = 0.00, 95% confidence interval (CI) 0.295-0.774] and 4.0 months (11.0 and 7.0 months. χ² = 11.73, p = 0.00. 95% CI 0.989-2.502), respectively, compared to the TA group. The risks of disease progression and mortality in the TAR group were reduced by 53.0% (hazard ratio (HR) = 0.470, 95% CI 0.294-0.753) and 49.3% (HR = 0.507, 95% CI 0.315-0.815) compared to the TA group. The OS and PFS rates at 1 and 2 years increased by 28.9% (97.8% and 68.9%, p = 0.00) and 20.0% (42.2% and 22.2%, p = 0.07) and 28.9% (42.2% and 13.3%, p = 0.00) and 15.6% (20.0% and 4.4%, p = 0.05), respectively, in the TAR group compared to the TA group. Most patients mainly presented with grade 1/2 tolerable acute AEs (p > 0.05). No AEs were related to radiotherapy, and no fatalities occurred. The results indicate that tislelizumab plus anlotinib and radiotherapy is a safe and effective treatment for advanced HCC. Trial registration: ChiCTR2000039022 (10/13/2020). Retrospective.