967P - Lenvatinib (L) versus sorafenib (S) second-line therapy in hepatocellular carcinoma (HCC) patients (P) progressed to atezolizumab plus bevacizumab (AB)

Background

This retrospective multicenter real-world study aims to compare outcomes reached by L and S second-line therapy in HCC P treated with first-line AB.

Methods

The overall cohort included 891 HCC P from 5 countries (Italy, Germany, Portugal, Japan, and the Republic of Korea) treated with AB in first-line setting. 53.0% of P had progressive disease after first-line therapy, of which 51.5% received a second-line treatment. Data from 137 P were available: 37.2% received S and 62.8% L.

Results

L second-line subgroup achieved a median overall survival (mOS) of 18.9 months (mo), significative longer (p = 0.01; HR: 2.24) compared to S subgroup that reached a mOS of 14.3 mo. After adjusting for positive clinical covariates at univariate analysis, multivariate analysis highlighted ALBI 1 grade [p < 0.01; hazard ratio (HR): 5.23] and L second-line therapy (p = 0.01; HR: 2.18) as positive prognostic factor for OS. Forest plot highlighted a positive trend in terms of OS in favor of P treated with L second-line regardless of baseline characteristics before first-line therapy. In particular, L second-line subgroup had a better OS compared to S second-line subgroup in male P, aged ≤ 70 years, with viral etiology, BCLC C stage, αfetoprotein < 400 ng/mL, Child-Pugh A, NLR < 3, ALBI 1 grade, performance status ≤ 1, presence of portal vein thrombosis. Regarding first-line outcomes, L second-line subgroup achieved a median progression-free survival (mPFS) of 3.5 mo, while S second-line subgroup reached a mPFS of 4.3 mo without any significative difference (p 0.42; HR: 1.15). There was no difference in overall response rate (L 26.1% vs. S 19.8%; p = 0.29) and disease control rate (L 76.8% vs. S 66.4%; p = 0.71) between the two subgroups. Among the group of P reaching a first-line PFS inferior to 6.0 mo, P treated with L second-line achieved a mOS of 17.0 mo significative longer (p = 0.02; HR: 2.24) compared to those treated with S second-line (9.2 mo). Within the group of P reaching a first-line PFS superior to 6.0 mo, there was no difference in mOS between the two subgroups (S 15.7 mo vs. L not reached; p = 0.12; HR: 2.41).

Conclusions

L second-line therapy is superior to S in HCC P progressed to first-line AB.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.