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 (29/71, 40.8% vs. 14/71, 19.7%, P = 0.006) and disease control rates (44/71, 62.0% vs. 22/71, 31.0%, 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.