Early lenvatinib dose intensity is associated with survival in super-older adults (≥80 years) with hepatocellular carcinoma: a real-world comparison with atezolizumab-bevacizumab.

Objective

To compare lenvatinib (LEN) and atezolizumab plus bevacizumab (Atezo + Bev) as first-line therapy in super-older adults (≥80 years) with hepatocellular carcinoma (HCC) and evaluate whether early relative dose intensity (RDI) is associated with outcomes.

Methods

This retrospective cohort study included super-older adults initiating LEN or Atezo + Bev between May 2018 and August 2025. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) and adverse events. Inverse probability of treatment weighting and multivariable Cox regression were performed. Within the LEN cohort, a day 56 landmark analysis evaluated the prognostic significance of 8-week RDI (RDI8 ≥ 75% vs. <75%).

Results

Median OS was 15.6 and 10.7 months with LEN and Atezo + Bev [hazard ratio: 0.77, 95% confidence interval (CI): 0.42-1.41], whereas median PFS was 6.73 and 9.73 months, respectively (hazard ratio: 1.18, 95% CI: 0.65-2.17). IPTW and multivariable analyses yielded similar results. Within the LEN cohort, RDI8 greater than or equal to 75% was independently associated with improved OS (30.8 vs. 14.7 months; adjusted hazard ratio: 0.23, 95% CI: 0.07-0.73, P = 0.013). Grade greater than or equal to 3 adverse events occurred in 37 and 50% of the LEN and Atezo + Bev cohorts, respectively.

Conclusion

Although LEN and Atezo + Bev showed no statistically significant difference in real-world survival in this exploratory cohort, these findings require validation in larger studies. Higher early LEN dose intensity was consistently associated with improved survival and may represent an important therapeutic consideration in super-older adults with HCC.