Abstract
INTRODUCTION: Atezolizumab plus bevacizumab significantly improved overall survival (OS) and progression-free survival (PFS) versus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in IMbrave150. Efficacy and safety in patient subpopulations with Vp4 portal vein tumor thrombosis (PVTT) and other high-risk prognostic factors are reported. METHODS: IMbrave150 was a global, randomized (2:1), open-label, phase 3 study in systemic treatment-naive patients with unresectable HCC; OS and PFS were co-primary endpoints. Exploratory analyses compared the efficacy and safety of atezolizumab 1,200 mg plus bevacizumab 15 mg/kg every 3 weeks versus sorafenib 400 mg twice daily in patients (i) with and without Vp4 PVTT alone and (ii) with and without high-risk prognostic factors. RESULTS: In patients with Vp4 PVTT, median OS was 7.6 months (95% CI: 6.0-13.9) with atezolizumab plus bevacizumab (n = 48) and 5.5 months (95% CI: 3.4-6.7) with sorafenib (n = 25; HR 0.62 [95% CI: 0.34-1.11]; descriptive p = 0.104). Median PFS in the respective arms was 5.4 months (95% CI: 3.6-6.9) and 2.8 months (95% CI: 1.5-5.3; HR 0.62 [95% CI: 0.35-1.09]; descriptive p = 0.094). In patients without Vp4, median OS was 21.1 months (95% CI: 18.0-24.6) with atezolizumab plus bevacizumab (n = 288) and 15.4 months (95% CI: 12.6-18.6) with sorafenib (n = 140; HR 0.67 [95% CI: 0.51-0.88]; descriptive p = 0.003). Median PFS in the respective arms was 7.1 months (95% CI: 6.1-9.6) and 4.7 months (95% CI: 4.2-6.1; HR 0.64 [95% CI: 0.51-0.81]; descriptive p < 0.001). The high-risk versus non-high-risk populations had similar outcome patterns. In the respective treatment arms, grade ≥3 treatment-related adverse events occurred in 43% and 48% of patients with Vp4 and 46% and 47% of patients without Vp4. CONCLUSION: Regardless of VP4 PVTT or other high-risk features of unresectable HCC, which have often resulted in exclusion from other front-line trials, patients benefited from atezolizumab and bevacizumab versus sorafenib.