Efficacy Of Apatinib In Transcatheter Arterial Chemoembolization (TACE) Refractory Intermediate And Advanced-Stage Hepatocellular carcinoma：A Propensity Score Matching Analysis

PURPOSE: This research aimed to compare the efficacy of combination treatment of transcatheter arterial chemoembolization (TACE) with apatinib versus TACE-alone for intermediate and advanced-stage hepatocellular carcinoma (HCC) cases refractory to TACE. PATIENTS AND METHODS: A total of 125 patients with TACE refractory intermediate or advanced-stage HCC were enrolled and classified as TACE-apatinib group and TACE-alone group. One-to-one matched pairs between two groups were generated using propensity score matching (PSM). Associations of treatment modality with overall survival (OS) and progression-free survival (PFS) were determined by Cox regression. Adverse effects (AEs) were compared between two treatment groups to assess the safety of apatinib. RESULTS: Before PSM analysis, the median OS and PFS were 17.0 and 7.0 months in the TACE-apatinib group, while 8.5 and 2.5 months in the TACE-alone group (P<0.05). After PSM analysis, 29 pairs of patients were generated with no significant difference in baseline characteristics. The median OS and PFS were 17.0 and 7.0 months in the TACE-apatinib group, while 10.7 and 2.0 months in the TACE-alone group (P<0.001). Multivariate analyses showed that TACE-apatinib treatment was a positive prognostic factor of both OS (hazard ratio [HR]=0.280, 95% confidence interval [95% CI] =0.158–0.499; P<0.001) and PFS (HR=0.348, 95% CI=0.223–0.544; P<0.001). Tumor size≥5 cm (HR=1.732, 95% CI=1.086–2.760; P=0.021), presence of portal vein tumor thrombus (HR=2.297, 95% CI=1.379–3.827; P=0.001) and distant metastasis (HR=1.962, 95% CI=1.223–3.148; P=0.005) were independent hazard factors of OS. Three patients in TACE-apatinib group appeared grade 3/4 AEs while their symptoms could be alleviated by dosage reduction and symptomatic treatments. CONCLUSION: TACE combined with apatinib demonstrated a superior therapeutic efficacy than TACE alone for improved OS and PFS toward the TACE refractory HCC. Apatinib could be recommended for HCC patients when TACE refractoriness occurs after further validation.