Final Results of TACTICS: A Randomized, Prospective Trial Comparing Transarterial Chemoembolization Plus Sorafenib to Transarterial Chemoembolization Alone in Patients with Unresectable Hepatocellular Carcinoma

Abstract

Introduction: Several clinical trials comparing the efficacy and safety of transarterial chemoembolization (TACE) plus molecular-targeted agents versus TACE alone revealed no clinical benefits in progression-free survival (PFS) or overall survival (OS). Here, we report the final OS analysis from the TACTICS trial, which previously demonstrated significant improvement in PFS with TACE plus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) (NCT01217034).

Methods: Patients with unresectable HCC were randomized to a TACE plus sorafenib group (N = 80) or a TACE alone group (N = 76). Patients in the combination treatment group received sorafenib 400 mg once daily for 2-3 weeks before TACE, followed by 800 mg once daily during on-demand conventional TACE sessions until time to untreatable progression. In this trial, TACE-specific PFS was used. TACE-specific PFS is defined as the time from randomization to progressive disease (PD) or death from any cause, and PD was defined as untreatable progression, caused by the inability of a patient to further receive or benefit from TACE for reasons that include intrahepatic tumor progression (25% increase vs. baseline) according to response evaluation criteria in cancer of the liver, the detection of extrahepatic spread, vascular invasion, or transient deterioration of liver function to Child-Pugh C after TACE.

Results: At the cut-off date of July 31, 2020, 131 OS events were observed. The median OS was 36.2 months with TACE plus sorafenib and 30.8 months with TACE alone (hazard ratio [HR] = 0.861; 95% confidence interval [CI], 0.607-1.223; p = 0.40, ΔOS, 5.4 months). The updated PFS was 22.8 months with TACE plus sorafenib and 13.5 months with TACE alone (HR = 0.661; 95% CI, 0.466-0.938; p = 0.02). Post-trial treatments with active procedures/agents were received by 47 (58.8%) patients in the TACE plus sorafenib group and 58 (76.3%) in the TACE alone group (p = 0.01). In post hoc analysis, PFS and OS benefit were shown in HCC patients with tumor burden beyond up-to-7 criteria.

Conclusions: In TACTICS trial, TACE plus sorafenib did not show significant OS benefit over TACE alone; however, clinical meaningful OS prolongation and significantly improved PFS was observed. Thus, the TACE plus sorafenib can be considered a choice of treatment in intermediate-stage HCC, especially in patients with high tumor burden. Trial Registration: NCT01217034.

Keywords: Hepatocellular carcinoma; Overall survival; Sorafenib; Transarterial chemoembolization; Up-to-7 criteria.

Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.

Figures

Fig. 1

Patient flowchart (CONSORT diagram).

Fig. 2

Kaplan-Meier curves of the co-primary endpoint of OS in the TACTICS trial. The median observation period was 33.4 months (range, 0.1–110.7) with 131 OS events.

Fig. 3

Forest plot of OS in subgroup analysis.

Fig. 4

TACE-specific PFS (a) and OS (b) in patients with tumor burden beyond the up-to-seven criteria. TACE-specific PFS (c) and OS (d) in patients with a tumor burden within the up-to-seven criteria.

Fig. 5

Kaplan-Meier curves of the co-primary endpoint of TACE-specific PFS updated as of the data cut-off date of July 31, 2020. Consistent with the primary analysis, significantly longer TACE-specific PFS was observed in the TACE plus sorafenib arm than in the TACE alone arm.

Fig. 6

Forest plot of updated TACE-specific PFS in subgroup analysis as of the data cut-off date of July 31, 2020.

Fig. 7

a Time to MVI. b Time to EHS. c Time to stage progression.