Radiotherapy enhances efficacy of PD-1 inhibitors in advanced hepatocellular carcinoma:A propensity-matched real-world study

Background:To address the need for immunotherapy in patients with advanced primary hepatocellular carcinoma(HCC),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 the efficacy of anti-programmed death receptor-1(PD-1)inhibitors in advanced HCC in real-world practice.Methods:Between August 2018 and June 2021,172 patients with advanced primary HCC were enrolled in the tertiary center(Zhongshan Hospital of Fudan University);95 were treated with a combination of RT and the inhibitor of PD-1(RT-PD1 cohort),and 77 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 71 propensity-matched pairs,median progression-free survival was 5.7 months in the RT-PD1 cohort vs.2.9 months in the PD1 cohort(P<0.001).Median overall survival was 20.9 months in the RT-PD1 cohort vs.11.2 months in the PD1 cohort(P=0.018).Compared with patients in the PD1 cohort,patients in the RT-PD1 cohort had significantly higher objective response rates(40.8%,29/71 vs.19.7%,14/71,P=0.006)and disease control rates(62.0%,44/71 vs.31.0%,22/71,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 primary HCC by improving survival outcomes without increased toxic effects.