LBA1 - Multicenter phase II trial of lenvatinib in patients with advanced hepatocellular carcinoma after progression on first-line atezolizumab plus bevacizumab (KCSG HB23-04)

Background

Atezolizumab-bevacizumab (AB) has been established as standard first-line therapy for unresectable hepatocellular carcinoma (uHCC). There is no global standard second-line therapy after progression on first-line AB, mainly because of the lack of prospective trials in this setting. We conducted a prospective multicenter trial of lenvatinib in patients (pts) with uHCC after progression on first-line AB.

Methods

This Korean Cancer Study Group (KCSG)-sponsored phase 2 study is an investigator-initiated study conducted in 13 centers in Korea. Eligibility criteria included confirmed HCC; disease progression on AB (at least after 2 cycles); Child A liver function; and ECOG performance status 0-1. Standard lenvatinib dosing for uHCC was used. Tumor response was evaluated every 8 weeks per RECIST v1.1. The primary endpoint is PFS, and secondary endpoints include OS, ORR, and AEs. A total of 50 pts were necessary to improve median PFS from 2 months to 4.5 months considering 1-sided a 0.1, power 80%, and 10% of follow-up loss.

Results

Between July 2023 and May 2024, a total of 50 pts were enrolled and received study treatment. Median age was 66 (range 32-86) years and 84.0 % were male. Viral hepatitis was the most common etiology (72%) and median PFS with prior AB was 6.5 months. Median follow-up duration was 6.5months (95% CI 5.0-7.7) and 29 (58%) and 13 (26%) events occurred for PFS and OS, respectively. Second-line lenvatinib provided median PFS of 5.4 months (95% CI, 5.3-5.6) months. The ORR per RECIST v1.1 was 12% and median OS was 8.6 months (95% CI 8.1-not assessable). Grade 3-4 AEs occurred in 46% of patients, with the most common AEs were hypertension (8%), anorexia (6%), proteinuria (6%) and AST elevation (6%). There was no new treatment-related death.

Conclusions

In this first prospective trial for lenvatinib after progression on first-line AB, Lenvatinib demonstrated clinically meaningful efficacy outcomes without a new safety signal. Lenvatinib should be considered one of the subsequent regimens after progression on prior AB. As OS data are premature, further follow-up analysis is required.

Clinical trial identification

NCT06138769.

Editorial acknowledgement

Legal entity responsible for the study

Korean Cancer Study Group.

Funding

Korean Cancer Study Group and Eisai.

Disclosure

C. Yoo: Financial Interests, Personal, Speaker, Consultant, Advisor: Eisai, AstraZeneca, Servier, BMS, MSD, HLB; Financial Interests, Personal, Research Funding: Eisai, AstraZeneca, Servier, Bayer; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim. H.J. Chon: Financial Interests, Personal, Advisory Board: Eisai, Roche, Bayer, ONO, MSD, BMS, Sanofi, Servier, AstraZeneca, BeiGene; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Eisai, Bayer, BMS, Servier, Sanofi, Dong-A ST. All other authors have declared no conflicts of interest.