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

作者：Kazuomi Ueshima, Kaoru Tsuchiya, Tatsuya Yamashita, Shigeo Shimose, Kazushi Numata, Yuzo Kodama, Shinji Itoh, Yasuhito Tanaka, Hidekatsu Kuroda, Kazuyoshi Ohkawa, Teiji Kuzuya, Masafumi Ikeda, Youhei Kooka, Hiroshi Aikata, Atsushi Hiraoka, Michihisa Moriguchi, Ryosuke Tateishi, Sadahisa Ogasawara, Kouji Yamamoto, Masatoshi Kudo · 发表于：Liver International · 年份：2025 · DOI：10.1111/liv.70379 · 被引用次数：3 · 研究领域：Colorectal Cancer Treatments and Studies、HER2/EGFR in Cancer Research、Cancer Immunotherapy and Biomarkers

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....