Donafenib plus transarterial chemoembolization (TACE) with or without anti–PD-1 antibodies for unresectable hepatocellular carcinoma second-line or later therapies: A retrospective multicenter study.

e16208 Background: Currently , there is still unsatisfactory effect of treatment regimen for patients with hepatocellular carcinoma (HCC) who have progressed after frontline combination therapy with immune checkpoint inhibitors. The Phase III clinical trial ZGDH3 has demonstrated donafenib improves overall survival (OS) in HCC patients. This study evaluated the efficacy and safety of donafenib combined with transarterial chemoembolization (TACE) ± programmed death-1 (PD-1) inhibitor for HCC second-line or later treatment. Methods: We retrospectively analyzed patients with HCC who received Donafenib combination therapy as second-line or above treatment at the first affiliated hospital Sun Yat-sen university, Shanghai oriental hepatobiliary hospital, Peking University Cancer Hospital, Sun Yat-sen memorial hospital and Henan cancer hospital between Jun 13, 2021 and Jun 21, 2025.The primary endpoint was objective response rate (ORR), and secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results: All of 41 patients were received donafenib combined with transarterial chemoembolization (TACE)±programmed death-1(PD-1) inhibitor. Second-line treatment accounted for 78.0%, and 22.0% used it as post-line treatment. 82.9% of the patients received the triple therapy with TACE, donafenib, and PD-1 inhibitor. Patients were classified as BCLC stage A (2.4%), B (22.0%) and C(75.6%). ORR were 34.1% per RECIST 1.1 and 61% per mRECIST, disease control rate (DCR)was 87%. In patients who had only received systemic therapy previously, ORR was 38.9% (RECIST 1.1), while in those who had previously undergone interventional therapy combined with systemic therapy, ORR was 30.4% (RECIST 1.1). The mPFS was 7.5 months and 12-month OS rate was 76.7%. 65.9% of patients had at least one treatment-emergent adverse events(TEAEs) and 7 patients (17.1%) had grade 3 and above TEAEs. During the treatment course, 56.4% of patients maintained stable liver function as assessed by the ALBI score, while 12.8% showed improvement. Conclusions: Donafenib combined TACE with or without PD-1 inhibitor has shown good efficacy and safety in the second-line or later therapies for HCC patients. ORR of the patients receiving different frontline treatment. ORR RECIST 1.1 n(%) mRECIST n(%) Overall (n=41) 14 (34.1) 25 (61.0) Frontline Therapy Interventional therapy with systemic therapy (n=23) 7 (30.4) 12 (52.1) With immunotherapy (n=19) 5 (26.3) 10 (52.6) Without immunotherapy (n=4) 2 (50.0) 2 (50.0) Systemic therapy alone (n=18) 7 (38.9) 13 (72.2) With immunotherapy (n=12) 4 (33.3) 8 (66.7) Without immunotherapy (n=6) 3 (50.0) 5 (83.3)