Enhanced Efficacy of Thalidomide‐Based Cocktail With Transarterial Chemoembolization in the Management of Unresectable Hepatocellular Carcinoma: A Multi‐Center Cohort Study

ABSTRACT This retrospective study was designed to evaluate the safety and efficacy of adding a thalidomide‐based cocktail (the TCC cocktail—comprising thalidomide, carmofur, and compound mylabris capsule) to transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC) in real‐world practice. Data from 433 unresectable HCC patients treated with TACE at four hospitals were collected (from March 2014 to May 2018, followed up to July 2023) and overall survival (OS), overall response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed. After 1: 2 propensity score matching (PSM), 114 patients in the cocktail group (TACE + TCC) were compared with 228 patients in the control group (TACE alone). The median OS of the cocktail group was significantly better than that of the control group ( p < 0.001; 42.5 vs. 12.5 months) after PSM. ORR (29.8% vs. 21.1%, p = 0.081) and DCR (79.8% vs. 61.8%, p < 0.001) at 6 months were also better in the cocktail group after PSM. Moreover, no life‐threatening AEs (grade 4 or 5) occurred in either group. In this retrospective cohort, the addition of the TCC cocktail to TACE was associated with improved survival and tumor response, with a manageable safety profile.