Efficacy of Locoregional Treatment for Oligo-Drug-Resistant Lesions during First-Line Atezolizumab plus Bevacizumab Therapy for Unresectable Hepatocellular Carcinoma: A Single-Center Retrospective Study.

[INTRODUCTION] Despite recent advancements, outcomes for unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (atezo/bev) remain suboptimal, with drug resistance posing a major challenge. This study evaluated the efficacy of additional locoregional treatments (LRTs) for oligo-atezo/bev-resistant lesions.

[METHODS] We retrospectively analyzed patients with intermediate-stage and advanced-stage HCC who developed drug-resistant lesions during first-line atezo/bev therapy. Patients were divided into two groups: the combination therapy group (n = 10) receiving additional LRT and the atezo/bev alone group (n = 26). Progression-free survival (PFS) 1 was measured from atezo/bev therapy initiation to progressive disease (PD) or death, whereas PFS2 was calculated from atezo/bev therapy initiation to PD of second-line therapy or death. The PFS1 in the combination therapy group was compared to the PFS1 and PFS2 in the atezo/bev alone group. Two analyses were performed for the PFS and overall survival (OS): one including the total cohort and the other restricted to those eligible for LRT upon the appearance of atezo/bev-resistant lesions. Changes in the hepatic reserve before and after LRT were also assessed.

[RESULTS] LRT, followed by continued atezo/bev therapy, safely eradicated drug-resistant lesions in the combination therapy group, without compromising the hepatic reserve. All patients in the combination therapy group transitioned to second-line treatment due to preserved hepatic reserve after PD. The PFS1 in the combination therapy group was longer than the PFS1 and PFS2 in the atezo/bev alone group in both the total cohort and LRT-eligible subgroup. Similarly, the OS in the combination therapy group was longer than in the atezo/bev alone group in both analyses.

[CONCLUSION] LRTs may provide a viable option for managing oligo-drug-resistant lesions during first-line atezo/bev therapy for unresectable HCC when safely administered.