Sorafenib Plus Transarterial Chemoembolization Improves Survival Outcomes, Response Among Patients With Recurrent Hepatocellular Carcinoma

According to a phase 3 trial, sorafenib plus transarterial chemoembolization (TACE) improved overall survival (OS), and progression-free survival (PFS) and objective response rate (ORR), compared with TACE alone among patients with recurrent intermediate-stage hepatocellular carcinoma (HCC).

The study authors wrote that while TACE is the optimal treatment for both recurrent and unresectable primary hepatocellular carcinoma, as recommended by most guidelines, recurrent disease is often more aggressive. To achieve better tumor control, the combination treatment of sorafenib and TACE “has been widely used in treating recurrent HCC.” There have been several retrospective studies reporting “on the superiority of [sorafenib plus TACE] to TACE alone in the survival of patients with recurrent HCC,” as study authors noted.

This open-label, randomized phase 3 trial enrolled 162 patients with recurrent intermediate-stage hepatocellular carcinoma following R0 hepatectomy with microvascular invasion. Patients were randomized on a 1-to-1 basis to receive either on-demand TACE (conventional, or drug-eluting bead TACE; n = 82), or sorafenib plus on-demand TACE. The primary end point for this study was OS, with secondary end points including PFS, ORR (based on modified RECIST criteria), and safety.

With a median follow-up duration of 37.5 months in the sorafenib plus TACE arm and 36.9 months in the TACE alone arm, the median OS in the sorafenib plus TACE arm was 22.2 months compared to 15.1 months in the TACE alone arm, representing a statistically significant improvement (hazard ratio [HR], 0.55; P < .001). The median PFS was 16.2 months vs 11.8 months (HR, 0.54; P < .001) respectively, and the ORR was 80.2% vs 58.0% (P = .002) respectively. The OS, PFS, and local tumor response rates were comparable between patients who underwent conventional TACE and those who underwent drug-eluting bead TACE.

Any grade adverse events were more common in the sorafenib plus TACE arm, but all adverse events were manageable with treatment. Sorafenib-related grade 3/4 adverse events included hand-foot skin reaction and hypertension. All patients recovered from all adverse events following either treatment or dose reduction. In the sorafenib plus TACE group, 69.1% of patients required a dose reduction and 46.9% required sorafenib interruption.

The study authors concluded that this study “observed [sorafenib plus TACE] to be clinically feasible and safe” with “moderate and manageable” adverse events among patients with recurrent intermediate-stage hepatocellular carcinoma after R0 initial hepatectomy with positive microvascular invasion. They added that this combination regimen “has the potential to be used effectively in these patients.”

Source:

Fan W, Zhu B, Chen S, et al. Survival in patients with recurrent intermediate-stage hepatocellular carcinoma: Sorafenib plus TACE vs TACE alone randomized clinical trial. JAMA Oncol. Published online: June 20, 2024. doi:10.1001/jamaoncol.2024.1831