ABSTRACT Background and Aim Combining systemic chemotherapy with transarterial chemoembolization (TACE) has demonstrated improved outcomes, with promising results for the efficacy of lenvatinib pretreatment combined with TACE in single‐arm studies involving patients with hepatocellular carcinoma (HCC). This study aimed to evaluate the efficacy of a scheduled upfront lenvatinib combined with a TACE regimen in patients with HCC, representing both the first study to comparatively analyze this approach and to focus specifically on patients unsuitable for TACE. Methods We conducted a multicenter retrospective study between 2018 and 2024, enrolling 41 patients with unresectable Barcelona Clinic Liver Cancer intermediate‐stage HCC who were considered unsuitable for TACE owing to factors such as exceeding the up‐to‐7 criteria, having infiltrative HCC, or multiple asynchronous recurrent HCC. Of these patients, 25 received upfront lenvatinib administration prior to TACE (LEN‐TACE group), followed by continuous lenvatinib and on‐demand TACE, and 16 received lenvatinib monotherapy. Results Radiological evaluation revealed significantly higher complete response (CR) and objective response rates (ORR) in the LEN‐TACE group than in the lenvatinib group. The median overall survival (OS) was not reached in the LEN‐TACE group, whereas it was 16.2 months in the lenvatinib monotherapy group, indicating a significantly superior OS in the LEN‐TACE group (hazard ratio HR: 2.99; 95% CI: 1.01–8.95; p = 0.0496). Superiority in both PFS and OS was also observed in the propensity score‐matched (PSM) cohort for the LEN‐TACE group. Conclusion Scheduled upfront lenvatinib combined with TACE is superior to lenvatinib monotherapy for intermediate‐stage HCC, particularly in patients unsuitable for TACE.
Taniki et al. (2026) studied this question.