Efficacy of immune checkpoint inhibitors plus molecular targeted agents after the progression of lenvatinib for advanced hepatocellular carcinoma

Abstract

Background: Lenvatinib is a standard first-line systemic therapy in advanced hepatocellular carcinoma (aHCC) and is widely used in all lines. However, the efficacy and safety of immune checkpoint inhibitors (ICIs) plus molecular targeted agents (MTAs) after the progression of lenvatinib treatment are unclear.

Objective: The aim of this study was to evaluate the anticancer effects of ICI plus MTA in patients with aHCC who progressed after lenvatinib.

Methods: We retrospectively included aHCC patients treated with ICI plus MTA after the progression of lenvatinib from two medical centers. Participants who continued lenvatinib treatment were classified into the "ICI+Lenva" group, while the "ICI+Others" group included patients receiving other MTAs. The efficacy endpoints were progression-free survival (PFS), post-progression survival (PPS), overall survival (OS), and tumor response following RECIST v1.1. Safety was evaluated according to Common Terminology Criteria for Adverse Events v5.0.

Results: In this study, 85 eligible aHCC patients were enrolled, including 58 in the ICI+Lenva group and 27 in the ICI+Others group. At a median follow-up time of 22.8 months, the median PPS and PFS were 14.0 (95% CI: 9.0-18.2) and 4.5 months (95% CI: 3.5-8.3), respectively. The objective response and disease control rates were 10.6% and 52.9%, respectively. No significant differences were observed in any of the efficacy endpoints between the two groups. Prolonged PPS was associated with Child-Pugh grade A, AFP < 400 IU/ml, and concomitant locoregional treatment. All patients experienced adverse events (AEs), but no fatal AEs were observed.

Conclusion: ICI plus MTA in aHCC patients after the progression of lenvatinib presented high antitumor activity and safety. Patients could continue lenvatinib treatment and receive ICIs as well as locoregional treatment to achieve better OS.

Keywords: efficacy; hepatocellular carcinoma (HCC); immune checkpoint inhibitor (ICI); lenvatinib; molecular targeted agent (MTA); safety.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Xie, Chen, Yang, Wang, Zhang, Wang, Wang, Zhang, Xue, Long, Li, Sun, Xun, Liu, Chen, Song, Yang, Lu, Mao, Sang, Lu and Zhao.

Figures

Figure 1

Survival outcomes for patients treated with ICI plus MTA after lenvatinib progression. (A) Progression-free survival for all patients; (B) Progression-free survival for the ICI+Lenva group and the ICI+Others group; (C) Post-progression survival for all patients; (D) Post-progression survival for the ICI+Lenva group and the ICI+Others group; (E) Overall survival for all patients; (F) Overall survival for the ICI+Lenva group and the ICI+Others group.

Figure 2

Survival outcomes for patients treated with ICI plus MTA after first-line lenvatinib progression. (A) Progression-free survival for patients after first-line or post-line lenvatinib progression; (B) Progression-free survival for the ICI+Lenva group and the ICI+Others group in first-line lenvatinib subgroup; (C) Post-progression survival for patients after first-line or post-line lenvatinib progression; (D) Post-progression survival for the ICI+Lenva group and the ICI+Others group in first-line lenvatinib subgroup; (E) Overall survival for patients after first-line or post-line lenvatinib progression; (F) Overall survival for the ICI+Lenva group and the ICI+Others group in first-line lenvatinib subgroup.

Figure 3

Risk factors for survival. (A) Multivariate Cox proportional hazard model for progression-free survival; (B) Multivariate Cox proportional hazard model for post-progression survival. ECOG, Eastern Cooperative Oncology Group; AFP, alpha-fetoprotein.