Stereotactic Body Radiotherapy Combined With Lenvatinib With or Without PD-1 Inhibitors as Initial Treatment for Unresectable Hepatocellular Carcinoma.

ABSTRACT

PURPOSE: The aim of this study was to compare the clinical benefit and safety of the triple combination of stereotactic body radiotherapy (SBRT), lenvatinib, and programmed cell death protein 1 (PD-1) inhibitors with the dual combination of SBRT and lenvatinib in patients with unresectable hepatocellular carcinoma (uHCC). METHODS AND MATERIALS Patients with uHCC who received SBRT in combination with lenvatinib and PD-1 inhibitors or SBRT in combination with lenvatinib alone as first-line treatment from October 2018 to July 2022 were reviewed in this study. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints were intrahepatic PFS, extrahepatic PFS, and objective remission rate. In addition, safety profiles were assessed by analyzing treatment-related adverse events between the two groups to assess safety profiles. RESULTS: In total, 214 patients with uHCC who received combination therapy were included in this retrospective study. Among them, 146 patients received triple combination therapy of SBRT, lenvatinib, and PD-1 inhibitors (SBRT-L-P group), and 68 patients received dual therapy of SBRT and lenvatinib (SBRT-L group). The median OS times of the 2 groups were 31.2 months and 17.4 months, respectively (P < .001). The median PFS time was significantly longer in the SBRT-L-P group than in the SBRT-L group (15.6 months vs 8.8 months, P < .001). Additionally, the median intrahepatic PFS (17.5 vs 9.9 months, P < .001) and extrahepatic PFS (20.9 vs 11.6 months, P < .001) were significantly longer in the SBRT-L-P group than in the SBRT-L group. The objective remission rate in the SBRT-L-P group was higher than in the SBRT-L group (63.0 vs 39.7%, P = .002). The incidence and severity of treatment-related adverse events in the SBRT-L-P group were comparable to those in the SBRT-L group. CONCLUSION: The use of both lenvatinib and PD-1 inhibitors with SBRT in patients with uHCC was associated with improved overall survival compared with lenvatinib and SBRT alone with a manageable safety profile.