Sorafenib combined with transarterial chemoembolization versus transarterial chemoembolization alone for advanced-stage hepatocellular carcinoma: a propensity score matching study

Abstract

Aims: The purpose of the present study was to compare the efficacies of transarterial chemoembolization (TACE) combined with sorafenib versus TACE monotherapy for treating patients with advanced hepatocellular carcinoma (HCC).

Methods: We enrolled 321 patients and selected 280 with advanced HCC (Barcelona Clinic Liver Cancer stage C) who underwent TACE therapy between February 2009 and February 2013. TACE alone (monotherapy group) was administered to 198 patients (70.7%), and the remaining 82 (29.3%) underwent repeat combined TACE and sorafenib therapy (combined group). To minimize selection bias, these latter 82 patients were matched using propensity-score matching at a 1∶2 ratio with 164 patients who received TACE monotherapy. The primary endpoints were overall survival (OS) and related subgroup analysis. The secondary endpoints were time to progression (TTP) and treatment-related adverse events.

Results: Of the respective patients in the combined and monotherapy groups, 64.6% and 49.2% had vascular invasion, 87.8% and 91.1% had extrahepatic metastasis, and 54.3% and 47.1% had both. In the propensity-score-matched cohort, the OS survival of the combined group was significantly higher compared with the monotherapy group (7.0 months vs. 4.9 months, respectively, P = 0.003). The TTP was significantly longer in the combined group (2.6 months vs. 1.9 months, respectively, P = 0.001). Subgroup analysis showed that the outcomes of patients with advanced HCC without main portal vein invasion who were treated with combined therapy were significantly better compared with those who received monotherapy (P<0.05). Univariate and subsequent multivariate analyses revealed that the addition of sorafenib was an independent predictor of favorable OS and TTP (adjusted hazard ratios, 0.63 and 0.62, respectively; P<0.05 for both).

Conclusion: Sorafenib plus TACE was more effective than TACE monotherapy for treating patients with advanced HCC without main portal vein invasion. Future trials with larger samples are required to validate these preliminary findings.

Figure 1. Patient selection.

Figure 2. Kaplan–Meier analysis of OS of the combined and monotherapy groups.

The Kaplan–Meier curves show the OS of the combined and monotherapy groups for propensity-matched patients. The median OS of the combined group was significantly longer compared with the monotherapy group in the matched model (7.0 months vs 4.9 months, respectively; P =  0.003).

Figure 3. Kaplan–Meier analysis of overall survival of subgroups of the combined group.

As shown in Figure 3, two subgroups showed significantly improved OS (the group of patients with portal vein branch thrombosis without tumor extrahepatic metastasis) compared with patients with portal vein thrombosis and tumor extrahepatic metastasisas follows: HR, 0.34; 95%CI, 0.16–0.73; P  = 0.005; Statistical data for the group of patients with tumor extrahepatic metastasis without portal vein thrombosis are as follows: HR, 0.46; 95%CI, 0.23–0.91; P  = 0.027). However, combined therapy did not significantly improve OS of the group with main portal vein thrombosis without tumor extrahepatic metastasis (HR, 1.07; 95%CI 0.54–2.13; P  = 0.848).

Figure 4. Kaplan–Meier analysis of OS of different subgroups of the combined and monotherapy groups.

(A) Kaplan–Meier curves for OS of the combined and monotherapy groups for patients with main portal vein thrombosis (5.8 months vs. 4.7 months, respectively; P = 0.06). (B) Kaplan–Meier curves for OS of the combined and monotherapy groups for patients with portal vein branch thrombosis (7.5 months vs 5.0 months, respectively; P = 0.032). (C) Kaplan–Meier curves for OS of the combined and monotherapy groups for patients with tumor metastasis (8.0 months vs. 3.0 months, respectively; P = 0.045). (D) Kaplan–Meier curves for OS of the combined and monotherapy groups for patients with portal vein thrombosis and tumor metastasis (4.9 months vs. 3.1 months, respectively; P = 0.19).

Figure 5. Kaplan–Meier analysis of TTP in the combined and monotherapy groups of propensity-matched patients.

Median TTP of the combined group was significantly longer compared with the monotherapy group in the matched model (2.6 months vs 1.9 months, respectively; P  =  0.001).