Abstract 50P
Background
HCC is a major global health issue, especially in China. Most cases are diagnosed at an advanced stage, making resection unfeasible. Systemic therapies like lenvatinib and bevacizumab have been used as treatment options, but emerging combination therapies are showing more promise. Triple therapy, which combines local and systemic treatments, has demonstrated higher response rates. However, the optimal combination of lenvatinib and bevacizumab in triple therapy for HCC remains uncertain.
Methods
A retrospective multicenter study of 371 Chinese patients with unresectable HCC (uHCC) from 21 centers between 2017-2023. Patients received lenvatinib or bevacizumab combined with anti-PD-1/L1 and interventional therapy (TACE/HAIC) as first-line treatment. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used for statistical analysis, along with subgroup analysis based on various clinical characteristics.
Results
The mean age was 55.3 years, with 85% male and 85% having HBV. Before adjustment, the lenvatinib group had a longer median OS (HR 0.536, P = 0.0016) and PFS (HR 0.649, P = 0.0075). After PSM, OS remained better for lenvatinib (HR 0.524, P = 0.0085), but PFS became similar between the groups (HR 0.808, P = 0.29). After IPTW, OS still favored lenvatinib. Subgroup analysis showed that patients aged ≤65 years, without a history of HBV infection, with BCLC-C stage, ALT ≤40 U/L, platelets ≥100×10ˆ9/L, or log 10 AFP ≥1.40 are more likely to benefit from lenvatinib-based triple therapy. There were no treatment-related deaths, and both groups had similar rates of serious adverse events (P = 0.895).
Conclusions
Lenvatinib-based triple therapy may prolong OS compared to bevacizumab, with certain subgroups of patients potentially benefiting more from lenvatinib. This study provides evidence for considering patient characteristics when choosing treatment for uHCC. Future research should focus on refining patient stratification and exploring biomarkers for predicting treatment response.
Clinical trial identification
This study involving human participants were reviewed and approved by Zhongshan Hospital, Fudan University (Approval No. B2022-195R).
Editorial acknowledgement
ZP, JC and WZ designed experiments and drafted the manuscript. DL, HL, TS, HS and WZ collected the cases. WZ approved the final version. The China Liver Cancer Study Group Yonug Investigators (CLEAP) provide the platform for data maintenance. All authors contributed to the article and approved the submitted version.
Legal entity responsible for the study
Zhongshan Hospital, Fudan University.
Funding
Tianjin Medical University Cancer Hospital, Precision Treatment Technology Construction Project for Cancer Surgery, ZLWKJZZL14. (2) Zhongguancun Precision Medicine Foundation, Medical and Health Public Welfare - Cancer Medical Research Special Project, ZGC-YXKY-ZL004.
Disclosure
All authors have declared no conflicts of interest.