Sorafenib extends PFS, but not OS, for HCC transcatheter arterial chemoembolisation

Presented by

Prof. Masatoshi Kudo, Kindai University, Osaka, Japan

Conference

ASCO GI 2021

Trial

Phase 2, TACTICS

The phase 2 TACTICS trial examined the combined use of transcatheter arterial chemoembolisation (TACE) and sorafenib in hepatocellular carcinoma (HCC) patients who were ineligible for resection or ablation treatment. The combination therapy prolongs progression-free survival (PFS) compared to TACE alone. However, adding sorafenib did not extend overall survival (OS).

Prof. Masatoshi Kudo (Kindai University, Osaka, Japan) presented the final OS data from TACTICS (NCT01217034), a randomised, open label, multicentre, phase 2 trial of TACE therapy in combination with sorafenib as compared with TACE alone in HCC patients [1]. Previous reports had already established that the median PFS was significantly longer in the TACE plus sorafenib arm than in the TACE alone group (25.2 vs 13.5 months; P=0.006). At that point, OS was immature with insufficient number of events [2].

Patients with unresectable HCC were randomised to TACE plus sorafenib (n=80) or TACE alone (n=76). Patients in the combination 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 (unTACEable) progression (TTUP). Co-primary endpoints were TTUP/PFS, and OS.

Unfortunately, the OS endpoint was not met. Median OS at this final analysis was 36.2 months in the TACE plus sorafenib arm, compared with 30.8 months in the TACE-alone arm (HR 0.86; 95% CI 0.61-1.22; P=0.40), representing a numerical benefit of 5.4 months. Updated PFS with this longer follow-up sustained significance was 22.8 month in the TACE plus sorafenib arm, compared with 13.5 months in the TACE-alone group (HR 0.66; 95%CI 0.47-0.94; P=0.02). There were no unexpected toxicities.

Prof. Kudo placed the data into perspective, stressing that the TACTICS trial clearly showed that TACE in combination with sorafenib should not be terminated at the point of intrahepatic tumour progression, when TACE is still deemed effective. Although there was a numerical OS benefit of a median 5.4 months, he speculated that the major reason that the OS did not reach significance was that many post-trial active treatments were performed in the control arm (76%), which implies that OS endpoint in TACE combination trial may not be feasible anymore in the current era of sequential therapy, with many active locoregional and systemic treatments. The results also suggest that pre-treatment of sorafenib before TACE and continued use of sorafenib after TACE will prolong the PFS and prolong the interval between each TACE session, providing the prevention of liver function deterioration often caused by TACE repetition. However, further large-scaled validation in a randomised controlled trial is warranted to establish the real benefits of the combined use of targeted agents with TACE.

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