TALENTACE supports atezolizumab + bevacizumab after TACE for HCC

Findings from the TALENTACE trial presented at ESMO GI 2025 support the combination of atezolizumab and bevacizumab after transarterial chemoembolization (TACE) for the treatment of individuals with systemically untreated, intermediate-to-high tumour burden, unresectable hepatocellular carcinoma (HCC).

“TALENTACE is the first phase III study to demonstrate the efficacy and safety of on-demand TACE combined with atezolizumab and bevacizumab, suggesting a new and effective treatment option [in this patient setting],” said Professor Dr Guohong Han from the Xi’an International Medical Center Hospital, Xi’an, China, during his presentation at ESMO GI 2025.

After a median follow-up of 26.3 months, the primary endpoint of investigator-assessed TACE-progression-free survival (PFS) was achieved when the combination regimen was administered after TACE as opposed to TACE alone (median 11.30 vs 7.03 months; hazard ratio [HR], 0.71, 95 percent confidence interval [CI], 0.55–0.92; p=0.009). Higher TACE-PFS rates were also reported with the former vs the latter at both 12 (48.46 percent vs 33.6 percent) and 18 (37.98 percent vs 29.85 percent) months.

TACE-PFS was defined as the time from randomization to untreatable progression or TACE failure/refractoriness or death by any cause. [ESMO GI 2025, abstract LBA2]

Of note, the Kaplan-Meier curves separated early but converged around 24 months and then diverged again. According to Han, the convergence may have been driven by the high amount of censoring, as approximately half of the patients were enrolled between January and August 2023 following COVID-19.

“Longer follow-ups are needed for more mature curves. Nonetheless, the current results show statistically significant and clinically meaningful improvement in PFS,” said Han.

A consistent pattern favouring the combination regimen plus TACE was observed in the PFS assessment per RECIST v1.1 (median 10.32 vs 6.37 months; HR, 0.64, 95 percent CI, 0.50–0.82). The 12- and 18-month PFS rates in the experimental arm were 41.96 percent and 31.66 percent, respectively. The corresponding rates in the control arm were 26.73 percent and 20.6 percent.

Save for the hepatitis C virus (HCV) aetiology subset, subgroup analysis mostly favoured the investigational regimen over TACE alone. The effects were more pronounced in the subgroups of patients with both hepatitis B virus (HBV) and HCV (HR, 0.44), with Vp1/2 (HR, 0.46), and those who had Barcelona Clinic Liver Cancer (BCLC) stage C disease (HR, 0.47).

The combination regimen plus TACE also yielded a higher overall response rate than TACE alone in both RECIST v1.1 (49.1 percent vs 33.9 percent) and RECICL (81.3 percent vs 66.7 percent) criteria.

Overall survival (OS) was still immature at the first interim analysis with only 38.6 percent survival events. The median OS was 34.53 months with the experimental regimen and 35.38 months with TACE alone (HR, 0.96, 95 percent CI, 0.68–1.34).

Safety profile

Compared with TACE alone, the combo regimen plus TACE was associated with higher rates of grade 3/4 treatment-related adverse events (TRAEs; 60.8 percent vs 40.5 percent) and serious TRAEs (25.9 percent vs 13.9 percent). A fifth of participants in the investigational arm withdrew from any study treatment due to AEs.

The most frequent TRAEs due to any treatment were proteinuria (45.8 percent), post-embolization syndrome (42.8 percent), and increase in aspartate aminotransferase (33.1 percent).

“[Nonetheless,] on-demand TACE combined with atezolizumab and bevacizumab show a safety profile that was generally manageable and consistent with the well-established profiles of the individual agents and the underlying disease, with no new safety signals identified,” said Han.

A new therapeutic paradigm for HCC?

TACE is the standard of care treatment for intermediate-stage HCC. [Hepatol 2023;78:1922-1965] “[However,] given the significant heterogeneity of intermediate-stage HCC, a single treatment approach like TACE may not be universally beneficial for patients within this stage,” said Han.

Han and colleagues thus sought to evaluate the ability of on-demand TACE combined with atezolizumab and bevacizumab to improve outcomes in patients with systemically untreated, intermediate-to-high tumour burden, unresectable HCC in China and Japan.

A total of 342 participants (median age 61 years, ~80 percent men) were randomized 1:1 to receive atezolizumab 1,200 mg plus bevacizumab 15 mg/kg intravenously Q3W within 14 days to 8 weeks after on-demand TACE or TACE alone. About 80 percent of the overall cohort had an ECOG PS score of 0 and a Child-Pugh score of 5. Most HCC cases were due to HBV (81 percent) and were classified as BCLC-B (~60 percent). All participants had a tumour burden score of ≥6.

The results establish the potential of on-demand TACE with atezolizumab plus bevacizumab as a new therapeutic paradigm for treatment-naïve unresectable HCC patients who have intermediate-to-high tumour burden, the researchers noted.

However, generalizability may be limited as most participants were Chinese (90 percent), noted discussant Dr Lorenza Rimassa from the IRCCS Humanitas Research Hospital, Milan, Italy. Rimassa called for more data with longer follow-up and more mature OS data.

Improved PFS an important endpoint

“If there is no prolongation of OS, then we may have to consider how important improved PFS is as an endpoint and use patient-reported outcomes as a way of assessing benefit in the face of TRAEs,” commented Professor Anna Saborowski from Hannover Medical School in Germany, in the ESMO press release.

“[Taken together, the] positive findings add to those from the placebo-controlled EMERALD-1 and LEAP-012 phase III trials, which demonstrated significant PFS improvement with TACE plus durvalumab/bevacizumab and TACE plus pembrolizumab/lenvatinib, respectively, albeit with design differences related to tumour burden, and the number and timing of TACE,” Saborowski added.