Atezolizumab-Bevacizumab in Very Elderly With Hepatocellular Carcinoma: Age Alone Is Not a Limiting Factor Except in ALBI Grade 3.

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

Methods: 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.

Results: Among 814 patients, 566 (69.5%) were <75 (median age 64, 84% male) and 248 (30.5%) ≥75 (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 (2.93-) and 2.3 months (1.63-) respectively. Immune-related AEs (IRAEs) 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 IRAEs (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).

Conclusion: Atezolizumab-Bevacizumab is effective and safe in patients ≥ 75 years but mALBI 3 warrants particular caution.

Clinical number: NCT06416683.