Durable Disease Control With Atezolizumab Plus Bevacizumab but Limited Post‐Progression Outcomes: A Multicenter Real‐World Study in Advanced Hepatocellular Carcinoma

INTRODUCTION: Atezolizumab plus bevacizumab (Atez/Bev) has become the standard first-line therapy for advanced hepatocellular carcinoma (HCC), but optimal second-line strategies remain unclear. This multicenter retrospective study compared survival outcomes and tumor control among first-line regimens and evaluated post-progression efficacy. METHODS: We retrospectively analyzed 1542 patients with advanced HCC who received sorafenib (SOR), lenvatinib (LEN), or Atez/Bev between 2009 and 2022. The main cohort (n = 612) excluded patients who underwent concomitant or inter-line locoregional therapy or entered clinical trials after first-line treatment. Overall survival (OS), progression-free survival (PFS), post-progression survival (PPS), duration of disease control (DDC), and duration of response (DOR) were estimated by Kaplan-Meier analysis and compared by the log-rank test. The impact of disease control and objective response on OS was assessed using time-dependent Cox models. RESULTS: Median OS was 15.4 months for SOR, 13.1 for LEN, and 20.6 for Atez/Bev (p = 0.002); Median PFS was 3.5, 5.7, and 7.5 months, respectively (p < 0.001); and median PPS was 10.8, 6.4, and 9.0 months, respectively (p = 0.049). Atez/Bev achieved the longest DDC (8.5 months) and DOR (22.1 months). Disease control and objective response were associated with improved OS (HR: 0.51/0.42 for SOR, 0.54/0.62 for LEN, 0.34/0.35 for Atez/Bev). After progression, median second-line PFS was 5.5 months for SOR, 2.5 for LEN, and 3.0 for Atez/Bev (p = 0.001). CONCLUSION: Atez/Bev provided superior survival and durable tumor control; however, post-progression outcomes remained unsatisfactory, underscoring the need for improved second-line approaches after Atez/Bev failure.