Randomized, open label, multicenter, phase II trial comparing transarterial chemoembolization (TACE) plus sorafenib with TACE alone in patients with hepatocellular carcinoma (HCC): TACTICS trial.

206 Background: There is no proven evidence that combination therapy of TACE with sorafenib (TS group) prolong progression-free survival (PFS) and/or overall survival (OS) compared to TACE alone (T group) in patients with unresectable HCC. Methods: In this randomized, open label, multicenter, comparative trial (NCT01217034), patients with unresectable HCC, Child-Pugh score ≤7, ECOG performance status 0-1, no vascular invasion (VI), no extrahepatic spread (EHS), size≤10 cm and number≤10 and adequate organ function were randomized 1:1 (stratification by institution, Milan criteria in or out, and number of previous TACE 0 or 1-2) to T or TS. In TS group, sorafenib 400 mg once daily was pretreated for 2-3 weeks prior to TACE followed by 800mg once daily during on-demand conventional TACE sessions until the time to untreatable progression (TTUP), which was defined as the time to the date of a state when TACE continuation is not possible due to untreatable tumor progression, deterioration to Child-Pugh C or appearance of VI/EHS. Co-primary endpoints are PFS and OS. Multiplicity is adjusted using a gatekeeping hierarchical testing. PFS event in this trial was defined as death or time to TTUP. Key secondary endpoints were time to progression and safety. PFS is expected to 40% extension from 18 months (control arm) to 25 months, target HR was 0.71, with a power of 0.80. Results: The trial was conducted in 33 institutions and a total of 156 patients were randomized to T (n = 76) or TS (n = 80). Median PFS in the T group and TS group was 13.5 and 25.2 months (HR = 0.59, 95%CI 0.41-0.87; p = 0.006), respectively. The number of OS events has not reached. Median TTP was 13.5 and 24.1 months in the T and TS groups (HR = 0.56, 95%CI 0.38-0.83; p = 0.004). Median TTUP was 20.6 and 26.7 months in the T and TS groups (HR = 0.57, 95%CI 0.35-0.92; p = 0.02), respectively. There was no unexpected toxicity. Conclusions: Sorafenib in combination with TACE significantly improved PFS over TACE alone in patients with unresectable HCC. Adverse events were consistent with the known safety profile with previous TACE combination trials. Clinical trial information: NCT01217034.