Regorafenib combined with immunotherapy and prognosis of unresectable hepatocellular carcinoma.

541 Background: To investigate the prognosis and influencing factors of patients with unresectable hepatocellular carcinoma (uHCC) receiving regorafenib in different treatment modes. Methods: A total of 227 patients with uHCC who received at least 2 cycles of regorafenib treatment in the Affiliated Hospital of Qingdao University between June 2018 and August 2022 were retrospectively collected through the Hospital Information System (HIS). 204 patients were finally enrolled by inclusion and exclusion criteria after screening. Results: The median follow-up was 25.9 (4.5-69.7) months. The median overall survival (OS) of 204 patients with uHCC was 27.7 (95%CI 21.98-33.42) months. The 1, 2, 3 and 5-year OS were 80.9%, 55.9%, 41.4% and 26.7%, respectively. Univariate analysis showed that combination with immune checkpoint inhibitor (ICI) and metabolic-associated complications were independent factors for survival benefit of regorafenib, while the Eastern Cooperative Oncology Group Performance Status (ECOG‐PS) scale = 2, undecreased Alpha-fetoprotein (AFP), macrovascular invasion and extrahepatic metastasis were independent risk factors for poor prognosis (P<0.05). Compared with 60 patients receiving regorafenib alone, 144 patients receiving regorafenib combined with ICI had a significant survival benefit (median OS, 16.9 vs. 31.5 months, respectively, P=0.006). The median OS of 153 patients receiving second-line therapy with regorafenib was 30.3 months. Among 51 patients receiving third or more lines of therapy with regorafenib, compared with 4 patients receiving regorafenib alone, 47 patients receiving regorafenib combined with ICI had a significant survival benefit (median OS, 9.4 vs. 24.1 months, respectively, P=0.000). Among 148 patients receiving local treatment, the median OS of patients with regorafenib combined with ICI (n=115) or without ICI (n=33) was 33.2 and 16.5 months, respectively (P=0.005). Conclusions: Regorafenib has a good prognosis in second-line treatment of uHCC. The OS of patients with regorafenib combined with ICI were significantly better than that of patients without ICI. The OS benefit of regorafenib combined with ICI was also equivalent in patients with third or more lines. The benefit of regorafenib combined with ICI was better for patients receiving local treatment.