Prior Radiotherapy Improves Progression-free Survival in Patients With Advanced Hepatocellular Carcinoma Treated With Tremelimumab-Durvalumab.

[BACKGROUND/AIM] Recent advances in systemic therapies, including immune checkpoint inhibitors (ICIs), have improved outcomes for patients with advanced hepatocellular carcinoma (HCC). Radiotherapy and ICI therapy have been reported to have synergistic effects. This study aimed to identify factors associated with the response to treatment with tremelimumab-durvalumab in patients with advanced HCC, including the impact of prior radiotherapy.

[PATIENTS AND METHODS] Forty-six patients with advanced HCC who received tremelimumab-durvalumab were retrospectively investigated. Intratumoral CD8 infiltration was evaluated in 23 patients who underwent liver tumor biopsy before starting tremelimumab-durvalumab.

[RESULTS] Sixteen of the 45 patients had received radiotherapy before starting chemotherapy (the RT group) and 29 had not (the non-RT group). The objective response rate was significantly higher in the RT group (56.3% 17.2%, =0.007), as was the disease control rate (75.0% 34.4%, =0.008). Median progression-free survival (PFS) was significantly longer in the RT group (14.6 months 2.7 months, =0.008). The adverse event rate was not significantly increased in the RT group. Intratumoral CD8 infiltration was significantly greater in the RT group [87.5% (7/8) 40.0% (6/15), =0.029]. Multivariate analysis identified prior radiotherapy to be a significant predictor of improved PFS (hazard ratio=0.290, 95% confidence interval=0.106-0.794, =0.016).

[CONCLUSION] Prior radiotherapy improves PFS in patients treated with tremelimumab-durvalumab for advanced HCC. The abscopal effect and up-regulation of immune mechanisms may contribute to improved outcomes.