Radiotherapy Enhances Efficacy of PD-1 inhibitors in Advanced Liver Cancer: A Real-world Data

Background: To address the need for immunotherapy in patient with advanced primary liver cancer, combination with radiotherapy (RT) has emerged as a promising strategy. In preclinical studies, irradiated tumors released tumor antigens to synergistically increase the antitumor effect of immunotherapy. Hence, we investigated whether RT enhances efficacy of anti-programmed death receptor-1 (PD-1) inhibitor in advanced liver cancer in real world practice. Methods Between August 2018 and June 2021, 180 patients with advanced primary liver cancer were enrolled, 87 were treated with a combination of RT and the inhibitor of programmed death receptor (RT-PD1 cohort) and 93 were administered anti-PD-1 therapy (PD1 cohort). The first cycle of PD-1 inhibitors was administered within 60 days or concurrently with RT. Propensity score matching for bias reduction was used to evaluate the clinical outcomes. Results Among 49 propensity-matched pairs after PSM, median progression-free survival was 8.1 months in the RT-PD1 cohort versus 3.0 months in the PD1 cohort ( P  < 0.001). Median overall survival was 21.7 months in the RT-PD1 cohort versus 13.3 months in the PD1 cohort ( P  = 0.023). Compared with patients in the PD1 cohort, patients in the RT-PD1 cohort had a significantly higher objective response rates (49.0% versus 22.4%, P  = 0.006) and disease control rates (71.4% versus 32.7%, P  < 0.001). The incidences of toxic effects were not significantly different between the two cohorts. Conclusions RT plus anti-PD-1 therapy is well tolerated. RT enhances the efficacy of anti-PD-1 therapy in patients with advanced liver cancer by improving survival outcomes without increased toxic effects.