Efficacy and safety of lenvatinib plus PD-1 inhibitor with or without transarterial chemoembolization in unresectable hepatocellular carcinoma.

Purpose: To compare the clinical benefit and tolerability of triple therapy of lenvatinib, programmed death 1 (PD-1) inhibitor, and transarterial chemoembolization (TACE) versus dual therapy of lenvatinib and PD-1 inhibitor in unresectable hepatocellular carcinoma (HCC) patients.

Methods: Between October 2018 and September 2021, patients with unresectable HCC who received triple therapy of lenvatinib, PD-1 inhibitor, and TACE or dual therapy of lenvatinib and PD-1 inhibitor participated in this study. The efficacy was evaluated by survival and therapeutic response, and the tolerability was evaluated by the frequency and severity of key adverse events (AEs).

Results: In total, 118 eligible patients with unresectable HCC who received combination therapy were included in this study. Among them, 60 patients received triple therapy of lenvatinib, PD-1 inhibitor, and TACE (L-P-T group), and 58 eligible patients received dual therapy of lenvatinib and PD-1 inhibitor (L-P group). Patients who received triple therapy had better overall survival (OS) [median, 29.0 vs. 17.8 months, p < 0.01] and progression-free survival (PFS) [median, 16.2 vs. 10.2 months, p < 0.01] than those who received dual therapy. The objective response rate (76.7 vs. 44.9%, p < 0.01) and disease control rate (96.7 vs. 75.9%, p < 0.01) in the L-P-T group were higher than in the L-P group, respectively. Multivariate analyses revealed that the treatment option and BCLC stage were independent prognostic factors for OS, while treatment option and tumor number were independent prognostic factors for PFS. The incidence and severity of AEs in the L-P-T group were comparable to those in the L-P group (any grade, 95.0 vs. 94.8%, p = 1.00; grade ≥ 3, 30.0 vs. 27.6%, p = 0.93).

Conclusion: Triple therapy of lenvatinib, PD-1 inhibitor, and TACE may achieve more favorable survival benefits than dual therapy of lenvatinib and PD-1 inhibitor in unresectable HCC patients with manageable safety profiles.