The Central Role of Liver Function at Treatment Initiation and Its Preservation at Progression for Post-Progression Survival After Atezolizumab Plus Bevacizumab in Advanced Hepatocellular Carcinoma

<b>Background/Objectives</b>: Atezolizumab plus bevacizumab (Atz+Bev) is widely used for advanced hepatocellular carcinoma (HCC), yet predictors of post-progression survival (PPS), a clinically meaningful endpoint reflecting the feasibility of treatment sequencing, remain unclear. We aimed to identify determinants of PPS and factors associated with successful transition to subsequent therapy after progressive disease (PD) on Atz+Bev. <b>Methods</b>: We retrospectively analyzed 132 patients with HCC who initiated Atz+Bev with Child-Pugh A and Eastern Cooperative Oncology Group performance status (ECOG PS) 0/1. PPS was defined as survival from radiological PD to death; tumor response was assessed by RECIST v1.1. <b>Results</b>: Among 132 patients treated with Atz+Bev, median progression-free and overall survival were 9.2 and 21.2 months. PD occurred in 97 patients, with a median PPS of 9.2 months. At PD, 76 patients (78.4%) maintained both Child-Pugh A and ECOG PS 0/1; 93.4% of these patients transitioned to subsequent therapy, compared with 38.0% of patients who did not maintain Child-Pugh A and ECOG PS 0/1. The median PPS values were 14.7 and 2.0 months, respectively (<i>p</i> < 0.0001). In this PD cohort, disease control achieved with subsequent therapy after radiological PD was associated with longer PPS (16.1 vs. 5.0 mosnths; <i>p</i> = 0.0002). ECOG PS 0, Child-Pugh A, absence of portal vein invasion, and AFP < 400 ng/mL at PD independently predicted prolonged PPS. A baseline Child-Pugh score of 5 independently predicted preservation of Child-Pugh A and ECOG PS 0/1 at PD. <b>Conclusions</b>: Initiating Atz+Bev under optimal liver function (Child-Pugh 5) and preserving hepatic reserve and performance status through progression are critical for enabling subsequent therapy and achieving longer PPS.