Atezolizumab-bevacizumab in very elderly with hepatocellular carcinoma: Age alone is not a limiting factor except in...

Evidence on atezolizumab plus bevacizumab (AtezoBev) in very elderly people with hepatocellular carcinoma (HCC) remains rare in the European ancestry population. We compared outcomes in patients aged ≥75 years with younger patients.

This multicenter retrospective study included patients treated with first-line AtezoBev for advanced HCC. Patients aged ≥75 years were matched 1:1 with those <75 years using propensity scores. Overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs) were analyzed.

Among 814 patients, 566 (69.5%) were <75 years (median age 64, 84% male) and 248 (30.5%) ≥75 years (median age 78, 86% male). After matching, 484 were analyzed. After a median follow-up of 28.0 months, OS and PFS were similar in ≥75 and <75 (15.4 vs. 16.07 months; p = 0.936), (7.2 vs. 6.5 months; p = 0.706) respectively. Age ≥ 75 years was not associated with PFS nor OS. In patients aged ≥75 years, modified albumin-bilirubin grade 3 (mALBI) was the only factor associated with disease progression (HR 4.37, 95% CI 2.04,9.37; p <0.001) and mortality (HR 5.62, 95% CI 2.47,12.8; p <0.001). In mALBI 3 median OS and PFS were 5.43 and 2.3 months, respectively. Immune-related AEs were less frequent in ≥75 including (22.1% vs. 36.9%; p <0.001) or excluding dysthyroidism (15.9% vs. 25.9%; p = 0.01). In univariate analysis, OS and PFS were longer in patients ≥75 years who developed hypertension (p = 0.04 and p = 0.09), proteinuria (p <0.0001 and p = 0.015) and Immune-related AEs (p = 0.02 and p = 0.007). Hypertension during treatment was associated with proteinuria (odds ratio = 13.1; 95% CI 4.1-42.4), without difference at baseline (p = 0.35).

AtezoBev is effective and safe in patients ≥75 years but mALBI 3 warrants particular caution.

Very elderly patients (≥75) are underrepresented in immunotherapy trials, leaving uncertainty about the benefit-risk of atezolizumab plus bevacizumab in this subgroup. In real-world practice, European ancestry patients ≥75 with advanced hepatocellular carcinoma are common. Our study indicates that atezolizumab-bevacizumab is generally safe and effective in this population, with mALBI grade 3 as a notable high-risk exception. Although retrospective, the use of propensity score methods mitigates confounding and supports the robustness of our conclusions.

NCT06416683.