The efficacy and safety study of thymosin α1 combined with PD-1 antibodies as adjuvant therapy in patients with hepatocellular carcinoma with high-risk recurrence factors after radical resection.

e16226 Background: Anti-PD-1 immunotherapy has revolutionized unresectable hepatocellular carcinoma (HCC) treatment. The efficacy of postoperative adjuvant therapy (PAT) using anti-PD-1 in treating HCC is currently the subject of extensive research. This study explored the efficacy and safety of anti-PD-1 antibodies combined with thymosin alpha-1 (Tα1) for patients with HCC and high-risk recurrent factors (HRRFs) post-hepatectomy. Methods: Data from 273 patients with HCC and HRRFs who underwent hepatectomy at Tongji Hospital (January 2019 to July 2022) were prospectively collected. Patients were nonrandomly divided into Tα1+ anti-PD-1 antibodies (65, 23.8%), anti-PD-1 antibodies (84, 30.8%), and control (no adjuvant therapy, 124, 45.4%) groups based on finances and willingness. After propensity score matching (PSM), recurrence-free survival (RFS) and overall survival (OS) were compared. Cox regression analysis identified the RFS- and OS-related prognostic factors, followed by subgroup analysis. Results: After PSM, 65 patients were matched. The anti-PD-1 antibodies + Tα1 group exhibited longer RFS than the anti-PD-1 antibodies (P = 0.014) and control (P < 0.0001) groups. The anti-PD-1 antibodies group had longer RFS than the control group (P < 0.0001). The anti-PD-1 antibodies + Tα1 (P = 0.00049) and anti-PD-1 antibodies groups (P = 0.0041) demonstrated longer OS than the control group. The 1- and 2-year RFS rates in the Tα1 + anti-PD-1 antibodies, anti-PD-1 antibodies, and control groups were 98.4%, 86.2%, and 49.2% (P < 0.001), and 80.2%, 65.8%, and 24.6% (P < 0.001), respectively. The corresponding 1-, 2-, and 3-year OS rates were 100.0%, 100.0%, and 84.6% (P < 0.001), 98.0%, 91.4%, and 69.0% (P < 0.001), and 91.3%, 86.8%, and 57.4% (P < 0.001), respectively. Multivariable analyses suggested that the Tα1 + anti-PD-1 antibodies treatment improved the RFS and OS more than the non-anti-PD-1 antibodies + Tα1 treatment (hazard ratio (HR): 0.174, 95% confidence intervals (CI): 0.089–0.340, P < 0.001 and HR: 0.240, 95% CI: 0.084–0.683, P = 0.008, respectively). Subgroup analysis demonstrated significant RFS and OS benefits for patients with HCC and vascular invasion treated with Tα1 + anti-PD-1 antibodies. Grade 1 and 2 toxicities included rash/pruritus (21.5%), diarrhea (18.5%), and reactive cutaneous capillary endothelial proliferation (RCCEP)(15.4%). Grade 3 toxicities included RCCEP (1.5%), diarrhea (1.5%), rash/pruritus (0.8%), edema (0.8%), hepatitis (0.8%), nausea/vomiting (0.8%), and hypothyroidism (0.8%). No grade 4/5 toxicities or severe adverse events were detected. Conclusions: Combining anti-PD-1 antibodies with Tα1 as adjuvant therapy is safe, improving postoperative prognosis in patients with HCC and HRRFs after hepatectomy, proving more effective than anti-PD-1 antibodies alone.