Real-world conversion surgery, survival outcomes, and safety of atezolizumab plus bevacizumab with TACE in unresectable hepatocellular carcinoma.

Abstract

e16223 Background: Hepatocellular carcinoma (HCC) remains challenging to manage once unresectable. Although atezolizumab plus bevacizumab is standard first-line therapy, its potential to enable conversion to curative resection is not well defined. We evaluated the efficacy and safety of atezolizumab plus bevacizumab combined with on-demand transarterial chemoembolization (TACE) in a real-world cohort, with a focus on surgical conversion. Methods: We conducted a multicenter real-world study of 121 patients with unresectable HCC treated with atezolizumab plus bevacizumab ± TACE. The primary endpoint was the objective response rate (ORR), and secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate, surgical conversion rates and safety. Results: Patients treated in the first-line setting achieved better outcomes than those receiving second-line therapy (ORR 47.3%, 53/112, vs 22.2%, 2/9), with longer median PFS (19.0 vs 8.8 months) and OS (35.3 vs 13.0 months). In the first-line cohort, patients receiving atezolizumab plus bevacizumab with TACE showed higher ORR (50.5%, 48/95, vs 29.4%, 5/17), longer median PFS (20.9 vs 8.0 months) and OS (35.3 vs 25.6 months) compared with those without TACE, with outcomes numerically exceeding historical GO30140 and IMbrave150 benchmarks. Successful R0 resection was achieved in 33.7% (32/95) of patients in the with-TACE group versus 5.9% (1/17) in the without-TACE group. Among resected patients, pCR occurred in 34.4% (11/32) and MPR in 68.8% (22/32; MPR, < 50% viable tumor cells). Among patients achieving MPR, RECIST responses included CR (n = 3), PR (n = 10), and SD (n = 9), indicating incomplete concordance between pathological and radiological assessments. A single tumor and higher CD8 + T-cell infiltration in baseline biopsy specimens were associated with a more favourable ORR. We further identified ECOG performance status, lower tumor burden, and pathological features of baseline biopsy specimens (higher CD4 + and CD8 + T-cell infiltration) as key factors associated with successful conversion to surgery. Treatment-related adverse events (TRAEs) occurred in 91.6% and 88.2% of patients in the with- and without-TACE groups, with grade 3/4 events in 54.7% and 52.9%, respectively; no grade 5 events or postoperative complications were observed. Conclusions: In this multicenter real-world cohort, on-demand TACE combined with atezolizumab plus bevacizumab enabled deep tumor responses and curative-intent resection in one-third of initially unresectable HCC patients. Baseline immune infiltration identified candidates most likely to benefit from conversion. These findings support a conversion-oriented strategy integrating locoregional and systemic therapy to bridge unresectable HCC toward surgical cure.