Atezolizumab Plus Bevacizumab for TACE-Unsuitable Intermediate-Stage HCC Beyond Up-To-7 Criteria: Final Analysis of REPLACEMENT.

BACKGROUND AND AIMS: The phase II REPLACEMENT study showed promising clinical benefit from atezolizumab plus bevacizumab in transcatheter arterial chemoembolization (TACE)-naïve patients with intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-7 criteria, meeting its primary endpoint of progression-free survival (PFS). Here, we report the final overall survival (OS) analysis. METHODS: Enrolled patients were naïve to TACE with unresectable intermediate-stage HCC beyond up-to-7 criteria, had Child-Pugh A, Eastern Cooperative Oncology Group performance status 0/1 and received no previous systemic therapy. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered every 3 weeks. The primary endpoint was the 6-month PFS rate by modified Response Evaluation Criteria in Solid Tumours for HCC (mRECIST); secondary endpoints included OS, PFS by RECIST version 1.1, objective response rate (ORR) and safety. RESULTS: Overall, 74 patients were enrolled between December 2020 and September 2021. At the clinical cut-off date (March 31, 2024), median follow-up was 33.6 months. Median PFS by mRECIST was 9.1 months (95% CI 7.1-10.2). Median OS was 33.8 months (95% CI 22.6-not estimable). ORR was 40.5% (95% CI 29.3-52.6), with 12.2% of patients having a complete response. Overall, 82.4% of patients received subsequent therapy. All-cause adverse events (AEs) were observed in 98.6% of patients, most commonly hypertension (71.6%) and proteinuria (54.1%). Grade 3/4 AEs occurred in 43.2% of patients; no Grade 5 AEs were reported. CONCLUSIONS: These results show that atezolizumab plus bevacizumab can be an alternative treatment option for patients with intermediate-stage HCC beyond up-to-7 criteria who are deemed unsuitable for TACE. TRIAL REGISTRATION: jRCTs071200051.