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

Abstract

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.

Keywords: ALBI score; atezolizumab plus bevacizumab; durvalumab‐tremelimumab; hepatocellular carcinoma; post‐ICI treatment.

FIGURE 1

Overall survival (OS) and progression‐free survival (PFS) of patients who received immunotherapy for unresectable hepatocellular carcinoma. (A) OS and PFS. (B) OS and PFS stratified by age group. (C) Liver‐related and non‐liver‐related death events stratified by age group.

FIGURE 2

Post‐immune checkpoint inhibitor (ICI) treatments and overall survival. (A) Breakdown of post‐ICI treatments assessed by age. (B) Overall survival according to post‐ICI treatments. CAB, cabozantinib; (D) durvalumab; DT, durvalumab + tremelimumab; HAIC, hepatic arterial infusion chemotherapy; LEN, lenvatinib; RAM, ramcirumab; REG, regorafenib; RFA, radiofrequency ablation; RT, radiation therapy; SOR, sorafenib; TACE, transcatheter arterial chemoembolization.

FIGURE 3

Overall survival stratified by the ALBI score and post‐ICI treatments in patients receiving immunotherapy. (A) Optimal cutoff for the ALBI score in predicting 12‐ and 24‐month survival. (B) Overall survival stratified by mALBI grades and post‐ICI treatments. (C) Overall survival stratified by mALBI grades and post‐ICI treatments assessed by age. ICI, immune checkpoint inhibitor; mALBI, modified albumin–bilirubin.

FIGURE 4

Immunotherapy algorithm for unresectable hepatocellular carcinoma, stratified by age and liver function. ALBI, albumin‐bilirubin grade; anti‐VEGF, anti‐vascular endothelial growth factor; ECOG PS, eastern cooperative oncology group performance status; HCC, hepatocellular carcinoma; ICI, immune checkpoint inhibitor; LE, late elderly; Non‐LE, non‐late elderly; OR, objective response; PD, progressive disease; QOL, quality of life; SD, stable disease; UAAE, unacceptable adverse event.