Atezolizumab-Bevacizumab with or without Cisplatin-based HAIC for Unresectable HCC: A Randomized Phase 2 Trial.

BACKGROUND: Atezolizumab plus bevacizumab (ATZ/BEV) is the global first-line standard treatment for unresectable hepatocellular carcinoma (HCC). However, the objective response rate (ORR) is approximately 30%. Hepatic arterial infusion chemotherapy (HAIC) with cisplatin may enhance its efficacy through locoregional cytoreduction and immunological modulation. We conducted a randomized phase 2 trial to evaluate whether sequential cisplatin HAIC plus ATZ/BEV (CDDP+ATZ/BEV) improves clinical outcomes compared to that with ATZ/BEV alone. METHODS: In this multicenter, open-label trial, patients with unresectable HCC were randomized 1:1 to receive cisplatin HAIC within 8 weeks before initiation of ATZ/BEV or ATZ/BEV alone. The primary endpoint was ORR. RESULTS: Between December 2021 and December 2024, 70 patients were enrolled in this study (CDDP+ATZ/BEV, n=35; ATZ/BEV, n=35). The primary endpoint, ORR, was numerically higher in the CDDP+ATZ/BEV group than in the ATZ/BEV group but did not reach statistical significance (45.7% vs 28.6%; p=0.095). Median progression-free survival (PFS) was longer in the CDDP+ATZ/BEV group (8.3 vs 6.6 months; HR 0.53; p=0.036), and median duration of response (DoR) was not reached vs 4.6 months (HR 0.4; p=0.11). The median overall survival (OS) was 28.1 vs 31.0 months (HR 0.95; p=0.88). Grade 3-4 treatment-related adverse events occurred in 20.0% and 22.9% of patients, respectively. CONCLUSIONS: The primary endpoint of ORR was not met. However, exploratory analyses demonstrated longer PFS without additional safety concerns. Further evaluation in phase 3 trials is warranted. CLINICAL TRIAL NUMBER: Japan Registry of Clinical Trials (jRCTs061210065).