AbstractBackgroundThere is no consensus on the optimal regimen for unresectable recurrent hepatocellular carcinoma (HCC), so this retrospective study aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib and PD‐1 inhibitors (T‐L‐P) versus TACE combined with lenvatinib (T‐L) or TACE alone.MethodData were collected from 204 patients with unresectable recurrent HCC who received T‐L‐P, T‐L, or TACE alone at three medical centers from January, 2019 to December, 2020 for analysis. The survival outcomes, tumor response, and adverse events were compared between three groups, and risk factors were further investigated.ResultsThe median overall survival in the T‐L‐P, T‐L, and TACE alone groups were not reached, 25.6, and 15.7 months, respectively (p< 0.001). The median progression‐free survival in the T‐L‐P, T‐L, and TACE alone groups were 24.1, 17.3, and 13.7 months, respectively (p< 0.001). The best objective response rate in the T‐L‐P, T‐L, and TACE alone groups were 70.4%, 48.9%, and 42.5%, respectively. The best disease control rate in the T‐L‐P, T‐L, and TACE alone groups were 100.0%, 97.8%, and 87.5%, respectively. There was no significant difference between the T‐L‐P and T‐L groups for Grade 3/4 adverse events.ConclusionT‐L‐P regimen was safe and superior to T‐L or TACE alone in improving survival for unresectable recurrent HCC patients.