On-Demand TACE Plus Atezolizumab/Bevacizumab Boosts PFS in Unresectable HCC

Transarterial chemoembolization (TACE) plus atezolizumab (Tecentriq) and bevacizumab (Avastin) prolonged investigator-assessed TACE-progression-free survival (TACE-PFS) vs TACE alone, according to data from the phase 3 TALENTACE trial (NCT04712643) presented during the 2025 ESMO Gastrointestinal Cancers Congress.¹

The median investigator-assessed TACE-PFS with TACE plus atezolizumab and 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 48.46% and 37.98%, respectively; in the TACE-alone arm, these respective rates were 33.60% and 29.85%.

The median PFS by investigator assessment and RECIST 1.1 criteria with TACE plus atezolizumab and bevacizumab was 10.32 months (95% CI, 8.51-11.93) vs 6.37 months (95% CI, 5.32-7.46) with TACE alone (HR, 0.64; 95% CI, 0.50-0.82). The 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,” Guohong Han, MD, of the Department of Gastroenterology, Xi’an International Medical Center Hospital, in Xi’an, China, said in late-breaking presentation.

Taking a Look at TALENTACE

The prospective, open-label, multicenter, phase 3 study enrolled patients with confirmed unresectable HCC who were candidates to receive TACE, including those with BCLC-A, BCLC-B, and BCLC-C for Vp1/2, and BCLC-C for an ECOG performance status of 1. Their sum of tumor maximum diameter plus tumor number needed to be at least 6, they needed to have an ECOG performance status of 0 or 1, and Child-Pugh A disease without extrahepatic spread. They could not have previously received systemic therapy or locoregional therapy to the target lesions.

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 alpha-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).

The primary end points of the trial were investigator-assessed TACE-PFS and overall survival (OS). Secondary end points were investigator-assessed PFS by RECIST v1.1 criteria, time to untreatable progression, time to progression, extrahepatic spread per Response Evaluation Criteria in Cancer of the Liver (RECICL), objective response rate (ORR), duration of response per RECICL and RECIST v1.1 criteria.

TACE-PFS was defined as the time from randomization to untreatable progression or TACE failure/refractoriness or death by any cause. For the statistical testing hierarchy, hypotheses will be formally tested on the primary end points of TACE-PFS and OS. 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 0.05.

Looking at the Analysis

A total of 342 patients were randomized; 171 were assigned to receive TACE plus atezolizumab and bevacizumab and 171 were assigned to receive TACE alone. In the TACE/atezolizumab/bevacizumab arm, 166 patients received all three 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 years (range, 30-89) in the TACE/atezolizumab/bevacizumab arm vs 60.0 years (range, 21-90) in the TACE-alone arm. Most patients were male (TACE/atezolizumab/bevacizumab, 79.5%; TACE-alone, 81.9%), had an ECOG performance 0 (81.8%; 87.1%), were from China (91.2%; 88.9%), had BCLC-B disease (58.5%; 61.4%), and had Child-Pugh score of 5 (81.3%; 78.4%).

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 and 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 and 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 RECICL with TACE plus atezolizumab and bevacizumab was 81.3%, which comprised a complete response (CR) rate of 39.2% and a partial response (PR) rate of 42.1% with stable disease (SD) and progressive disease (PD) rates of 11.7% and 3.5%, respectively; in the TACE arm, the ORR per RECICL was 66.7%, which comprised a CR rate of 28.1% and PR rate of 38.6%; SD and PD rates were 12.9% and 14.0%, respectively. ORR by RECIST v1.1 criteria with TACE plus atezolizumab and bevacizumab was 49.1%, which included a CR rate of 3.5% and a PR rate of 45.6%; SD and PD rates were 35.1% and 11.7%, respectively. ORR by RECIST v1.1 criteria with TACE alone was 33.9%, which comprised a CR rate of 4.1% and a PR rate of 29.8%; the SD rate was 34.5% and a PD rate was 24.0%.

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 and bevacizumab arm (n = 166) experienced at least 1 AE vs 99.4% of those in the TACE-alone arm (n = 173), with 100% and 97.7% of AEs related to treatment. Treatment-related grade 3 or 4 AEs occurred in 60.8% of those in the TACE combination arm vs 40.5% of those in the TACE-alone arm; 41.6% vs 40.5% were related to TACE, 27.7% were related to atezolizumab, and 38.6% were related to bevacizumab. Grade 5 AEs occurred in 4.2% of those in the TACE combination arm vs 2.9% of those in the TACE-alone arm; 3.0% vs 1.7% were related to treatment. Serious AEs occurred in 40.4% and 23.7% of those in the TACE combination and 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 TACE-alone arm, these respective percentages were 2.3% and 2.3%.

The most common treatment-related AEs were proteinuria, post-embolization syndrome, increased aspartate aminotransferase, decreased platelet count, hypoalbuminemia, hypertension, increased alanine aminotransferase, abdominal pain, pyrexia, and increased blood bilirubin.

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

Disclosures: Han disclosed receiving research grants from Shanghai Roche Pharmaceuticals, Co. Ltd; Bayer; Sirtex; Boston Scientific; and MSD. Lecture fees were received from Roche, Bayer, Gore, MSD, AstraZeneca, Sirtex, Bristol Myers Squibb, Boston Scientific, and Eisai. He does advisory consulting for Roche, Bayer, AstraZeneca, Boston Scientific, Gore, and MSD. The TALENTACE study is sponsored by Shanghai Roche Pharmaceuticals Ltd.

Reference

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.