Efficacy and safety of immune checkpoint inhibitors in Child-Pugh B and C hepatocellular carcinoma: Impact of treatment line, local therapy and bevacizumab combination.

Abstract

e16175 Background: The safety and efficacy of immune checkpoint inhibitors (ICI) in Child-Pugh (CP)-B and CP-C hepatocellular carcinoma (HCC) patients remain uncertain. In a multidisciplinary system a considerable number of patients will belong to this population and do not qualify for standard of care ICI-based regimens. This study presents a retrospective review of ICI in this specific population at our institution. Methods: This study included HCC patients who received at least one ICI dose between 1/1/2017 and 6/30/23 at Ohio State University. Clinical and pathological characteristics of interest were extracted through chart review. Survival outcomes assessed in this study include progression-free survival (PFS; date of first dose of ICI (Fd-ICI) to progression or death (D) or loss of follow-up (L-f/u)), overall survival (OS; date of diagnosis to D or L-f/u), and ICI-specific OS (OS-ICI; Fd-ICI to D or L-f/u). Kaplan-Meier methods were used to estimate PFS, OS-ICI, and OS survival distributions. Median survival times were calculated and compared between groups using the Wilcoxon test. Results: We had 25 patients (19 CP-B and 6 CP-C) in the study cohort (SC) with a median age of 67 years (range: 48-84), 72% males and 88% Caucasians. Most of them (96%) had ascites, and 40% had hepatic encephalopathy at the time of ICI initiation. Seven patients had tyrosine kinase inhibitors, and 15 had local therapy (LT) before ICI. Most received single-agent ICI (n = 17), while 8 had it combined with bevacizumab (BEV). Median doses of ICI for the group were 3 (range, 1-25) and were better in CP-B (4, 1-25) than in CP C (1, 1-4) population. The group's median PFS, OS-ICI, and OS (in days) were 159, 222, and 439, respectively. The CP-B subgroup had better median PFS (242 vs. 41 days, p = 0.0002) and median OS-ICI (235 vs. 50 days, p = 0.0046) than CP-C. However, the median OS had no significant difference (497 vs. 290 days, p = 0.4). BEV combination improved the OS-ICI (242 vs. 127 days, p = 0.04) but not PFS or OS for the SC (CP-B + C). Additionally, ICI in the second line or more (583 vs. 244, p = 0.02) and specifically after LT (575 vs. 252 days, p = 0.02) improved the OS of this study cohort. Similar findings were noted in the CP-B subgroup (line - 575 vs. 252 days, p = 0.02 and LT - 678 vs. 293 days, p = 0.02). Only two patients experienced grade 3 immune-related adverse events (dermatitis and colitis); no complications were associated with BEV. Conclusions: ICIs can be safely and effectively used in CP-B patients with advanced HCC, particularly after LT and in second-line or later settings. CP-C patients derive limited benefit, highlighting the need for cautious selection. Combining BEV with ICIs is safe and may offer survival benefits in this challenging population.