Predictive factors for the benefit of triple‐drug transarterial chemoembolization for patients with unresectable hepatocellular carcinoma

BACKGROUND: Compared with single‐drug TACE, our previous phase III study demonstrated that triple‐drug transarterial chemoembolization (TACE) prolonged overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC). The aim of this study was to find which patients can benefit from the triple drugs TACE compared with single‐drug TACE. METHODS: Patients in the triple‐drug TACE arm received sponge embolization and emulsions composed of 50 mg epirubicin, 50 mg lobaplatin, 6 mg mitomycin C, and lipiodol, while patients in the single‐drug TACE arm received sponge embolization and emulsions composed of 50 mg epirubicin and lipiodol. From July 2007 to November 2009, 244 patients (224 men and 20 women; age ranged from 21 to 75 years) from our phase III study formed the initial cohort. From January 2010 to June 2015, external validation cohort was composed of 449 patients (411 men and 38 women; age ranged from 18 to 75 years) from another institution. The validation cohort after propensity score matching (PSM) (n = 374) was analyzed. Cox proportional hazard model was used to evaluate the interaction term between treatments for each subgroup. This retrospective study was approved by the institutional review board at each center. RESULTS: No difference was observed in the baseline characteristic of three cohorts. This exploratory analysis showed that triple‐drug TACE brought a survival benefit in the initial cohort, validation cohort (before PSM), and validation cohort (after PSM) compared with single‐drug TACE. The outcomes of three cohorts all showed that a significantly greater OS triple‐drug chemotherapy benefit versus single‐drug chemotherapy was seen in patients with large tumors (larger than 10 cm) while no survival difference was seen in patients with small tumors (10 cm or smaller). CONCLUSIONS: Triple‐drug TACE seems to benefit patients with HCC larger than 10 cm in particular compared with single‐drug TACE.