Real-world experience of lenvatinib-based therapy in patients with advanced hepatocellular carcinoma.

Background: Given the significant advancements in the management of hepatocellular carcinoma (HCC) and the emergence of novel treatment approaches, establishing reliable predictors has become crucial for optimizing patient selection and therapeutic sequencing in HCC. In this study, we aimed to investigate the prognostic factors and treatment efficacy associated with lenvatinib-based therapy.

Methods: We retrospectively enrolled 53 patients receiving lenvatinib monotherapy, and 19 patients receiving lenvatinib plus immune checkpoint inhibitor combination therapy as their first-line systemic treatment for unresectable HCC at a single medical center. We employed univariate and multivariate Cox regression analyses to ascertain the factors influencing survival in these cohorts.

Results: For lenvatinib monotherapy and the combination therapy, the objective response rates were 30.2% and 63.2%, respectively (P=0.03); the median progression-free survival (PFS) durations were 7 months [95% confidence interval (CI): 4.5-9.5] and 12 months (95% CI: 6.4-17.6), respectively (P=0.74); and the median overall survival (OS) was not reached in either group (P=0.93). Although patients receiving the combination therapy had a greater treatment response, no significant survival differences were observed between the lenvatinib monotherapy and combination therapy subgroups, even after inverse probability of treatment weighting (IPTW). Patients who received lenvatinib monotherapy could be stratified based on a combination of albumin-bilirubin (ALBI) grade (either grade 1 or 2a) and a neutrophil-lymphocyte ratio (NLR) of ≤5.8. Compared to the other subgroups combined, those who met both of these criteria exhibited PFS with a hazard ratio (HR) of 0.382 (95% CI: 0.168-0.871; P=0.02), corresponding to 11 and 5 months, respectively; and an OS (HR: 0.198, 95% CI: 0.043-0.920; P=0.04) of not reached versus 12 months, respectively, according to multivariate Cox regression analysis.

Conclusions: In our study cohort, there were no statistically significant differences observed in the survival rates between patients treated with lenvatinib monotherapy and those treated with a combination of lenvatinib and immunotherapy. The incorporation of ALBI grade and NLR facilitates the stratification of survival outcomes in patients with unresectable HCC undergoing lenvatinib monotherapy.