Effect of Immunotherapy on Late Elderly Patients With Unresectable Hepatocellular Carcinoma: A Real-World Clinical Study.

Background/aim: The global aging population includes an increasing number of elderly patients with hepatocellular carcinoma (HCC). This study aimed to clarify the real-world outcomes, prognostic factors, and appropriate administration indicators for immunotherapy in elderly HCC patients.

Methods: This retrospective multicenter study analyzed 286 patients with unresectable HCC who received first-line immunotherapy (atezolizumab-bevacizumab or durvalumab-tremelimumab) between November 2020 and January 2024. Patients were categorized into the late elderly (LE; ≥ 75 years, n = 117) and non-late elderly (non-LE; ≤ 74 years, n = 169) groups. Baseline characteristics, overall survival (OS), progression-free survival (PFS), and prognostic factors were evaluated.

Results: The LE group had significantly poorer performance status, lower albumin-bilirubin (ALBI) scores, lower alpha-fetoprotein (AFP) and alanine transaminase levels, higher creatinine levels, and were significantly less likely to receive post-immune checkpoint inhibitor (ICI) treatment compared with the non-LE group (56.2% vs. 38.4%, p = 0.0038). Median OS and PFS for the LE group were 25.6 and 10.5 months, respectively. The LE group demonstrated a comparable disease control rate (82.0%) and safety profile. The ALBI score was a significant prognostic factor for both groups. Post-ICI treatment significantly improved OS only in the non-LE group, even after propensity score matching for ALBI score and AFP levels.

Conclusions: Immunotherapy is effective and well-tolerated in LE patients with unresectable HCC, particularly in those with preserved liver function (mALBI grade 1/2a). Post-ICI treatment significantly benefits non-LE patients, with limited impact on LE patients, highlighting the need for therapeutic strategies based on age and liver function.