TACE Combination Surpasses Monotherapy in HCC

Adding the monoclonal antibody atezolizumab (Tecentriq) and bevacizumab (Avastin) to transarterial chemoembolization (TACE) prolonged investigator-assessed TACE progression-free survival (TACE-PFS) vs TACE alone, according to data from the phase 3 TALENTACE trial (NCT04712643). These data were presented during the 2025 European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Congress.¹

The median PFS with TACE plus atezolizumab/ bevacizumab (n = 171) was 11.30 months (95% CI, 7.52–15.01) vs 7.03 months (95% CI, 5.32–8.41) with TACE alone (n = 171), meeting the primary end point (HR, 0.71; 95% CI, 0.55–0.92; P =.009). In the TACE plus atezolizumab/bevacizumab arm, the 12- and 24-month TACE-PFS rates were 48.46% and 37.98%, respectively; in the TACE-alone arm, the rates were 33.60% and 29.85%, respectively.

The median PFS by investigator assessment and RECIST 1.1 criteria was 10.32 months (95% CI, 8.51–11.93) with TACE plus atezolizumab/ bevacizumab vs 6.37 months (95% CI, 5.32–7.46) with TACE alone (HR, 0.64; 95% CI, 0.50–0.82). T he 12- and 18-month PFS rates in the TACE plus atezolizumab/bevacizumab arm were 41.96% and 31.66%, respectively; in the TACE-alone arm, these rates were 26.73% and 20.60%, respectively.

“TALENTACE is the first phase 3 study to demonstrate the efficacy and safety of on-demand TACE combined with atezolizumab and bevacizumab, suggesting a new and effective treatment option for patients with systemically untreated, intermediate to high tumor burden, unresectable HCC [hepatocellular carcinoma],” Guohong Han, MD, of the Department of Gastroenterology at Xi’an International Medical Center Hospital in China, said in a late-breaking presentation.

TALENTACE Details

The prospective, open-label, multicenter, phase 3 study enrolled patients with confirmed unresectable HCC who were candidates to receive TACE, including those with Barcelona Clinic Liver Cancer stage A (BCLC-A), BCLC-B, BCLC-C for Vp1/2, and BCLC-C for an ECOG performance status of 1. The patients’ sum of tumor maximum diameter plus tumor number needed to be at least 6, and they needed to have an ECOG performance status of 0 or 1 and Child-Pugh A disease without extrahepatic spread.

Patients (n = 342) were randomly assigned 1:1 to receive on-demand TACE followed by 1200 mg of atezolizumab and 15 mg/kg of bevacizumab every 3 weeks or underwent observation in the control arm. Stratification factors included baseline α-fetoprotein (< 400 ng/mL vs ≥ 400 ng/mL), prior locoregional therapy except curative resection and ablation (yes, TACE vs yes, other locoregional therapy vs no), baseline Vp1/2 (yes vs no), and geographic region (China vs Japan).

Han clarified that TACE-PFS and OS will be tested sequentially, with the overall type I error controlled at a 2-sided significance level of .05. Looking at the Analysis A total of 342 patients were randomly assigned; 171 were assigned to receive TACE plus atezolizumab/ bevacizumab, and 171 were assigned to receive TACE alone. In the TACE plus atezolizumab/ bevacizumab arm, 166 patients received all 3 components, 4 received only TACE, and 1 did not receive any treatment; 73 patients discontinued the study. A total of 171 patients comprised the intention-to-treat (ITT) population, and 166 comprised the safety set. In the TACE-alone arm, 169 received TACE alone, and 2 did not receive any treatment; 81 discontinued the study. A total of 171 patients comprised the ITT population, and 173 comprised the safety set.

The median time from randomization to the data cutoff for the first interim analysis was approximately 26 months, and the minimum follow-up was 18.4 months. The median patient age was 62.0 years (range, 30-89) in the triple combination arm vs 60.0 years (range, 21-90) in the TACEalone arm. Most patients were men (TACE/ atezolizumab/bevacizumab, 79.5%; TACE alone, 81.9%), had an ECOG performance score of 0 (81.8%; 87.1%), and were from China (91.2%; 88.9%).

Additional Efficacy Data

OS data were immature at the time of the analysis, with only 38.6% of events reported. The median OS was 34.53 months (95% CI, 26.78–not evaluable [NE]) with TACE plus atezolizumab/bevacizumab vs 35.38 months (95% CI, 29.50–NE) with TACE alone (HR, 0.96; 95% CI, 0.68–1.34; 2-sided P =.793). The 12- and 18-month OS rates in the TACE plus atezolizumab/bevacizumab arm were 87.95% and 78.13%, respectively; in the TACE-alone arm, these rates were 84.30% and 73.92%, respectively.

The ORR per RECIST 1.1 criteria with TACE plus atezolizumab/bevacizumab was 49.1%, which included a CR rate of 3.5% and a PR rate of 45.6%, with SD and PD rates of 35.1% and 11.7%, respectively. In the TACE-alone arm, the ORR by RECIST 1.1 criteria was 33.9%, which comprised a CR rate of 4.1% and a PR rate of 29.8%, with SD and PD rates of 34.5% and 24.0%, respectively.

Safety Spotlight

“On-demand TACE combined with atezolizumab and bevacizumab showed a safety profile consistent with the well-established profiles of the individual agents and the underlying disease,” Han said.

All patients in the TACE plus atezolizumab/bevacizumab arm (n = 166) experienced at least 1 adverse effect (AE) vs 99.4% of those in the TACE-alone arm (n = 173), with 100% and 97.7% of AEs related to treatment. Serious AEs occurred in 40.4% and 23.7% of those in the TACE combination and TACE-alone arms, respectively; they were related to treatment for 25.9% and 13.9% of cases, respectively.

In the TACE combination arm, 21.1% experienced AEs that led to withdrawal from any study treatment, and 58.4% experienced AEs leading to any interruption of study treatment or TACE delay; in the TACEalone arm, these respective percentages were 2.3% and 2.3%.

The most common treatment-related AEs were proteinuria, postembolization syndrome, increased aspartate aminotransferase, decreased platelet count, hypoalbuminemia, and hypertension.

“No new safety signals were identif ied,” Han said. “The safety profile of on-demand TACE combined with atezolizumab plus bevacizumab was generally manageable.”

REFERENCE:

1. Dong J, Han G, Ogasawara S, et al. TALENTACE: a phase III, open-label, randomized study of on-demand TACE combined with atezolizumab + bevacizumab (atezo+bev) or on-demand TACE alone in patients with systemically untreated intermediate-to-high tumor burden unresectable HCC. Presented at: 2025 ESMO Gastrointestinal Cancers Congress; July 2-5, 2025; Barcelona, Spain. Abstract LBA2.