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

ABSTRACT 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.