Safety and Efficacy of Lenvatinib Treatment in Child–Pugh A and B Patients with Unresectable Hepatocellular Carcinoma in Clinical Practice: A Multicenter Analysis

Abstract

Purpose

To assess the safety, efficacy and prognostic impact of clinical factors related to lenvatinib treatment in Child-Pugh class A (CP-A) and class B (CP-B) patients with unresectable hepatocellular carcinoma (u-HCC).

Methods

Patients with u-HCC who were treated with lenvatinib at multiple centers in Japan were retrospectively analyzed for treatment outcomes according to their respective CP status. Radiological objective response (OR) was assessed using modified response evaluation criteria in solid tumors (mRECIST) guidelines.

Results

Baseline demographic parameters were comparable between 126 (69.6%) patients with CP-A disease and 55 patients (30.4%) with CP-B disease. Frequency of lenvatinib-related adverse events, including decreased appetite (P=0.034), diarrhea (P=0.040), elevated serum bilirubin (P=0.016) and vomiting (P=0.009), were higher in CP-B than in CP-A patients. Relative dose intensity (RDI) was significantly higher in CP-A (0.69) than CP-B patients (0.50, P <0.001). Furthermore, OR rate (44.0%) was markedly higher in CP-A5 patients as compared to CP-A6 (25.5%), CP-B7 (22.2%), and CP-B8 patients (5.3%), respectively (P=0.002). In multivariable analysis, performance status (0 vs 1, 2, P=0.026), CP class (A vs B, P=0.045) and RDI (≥0.7 vs <0.7, P=0.034) were identified as factors associated with response to lenvatinib treatment. Overall survival (OS) at 12 months was significantly different between CP-A (66.3%) and CP-B patients (30.0%, P=0.002), and between CP 5–7 (59.2%) and CP 8 patients (34.8%, P=0.003). In multivariable analysis, CP class (A vs B, P=0.007) and Barcelona clinic liver cancer (BCLC) stage (B vs C, P=0.002) were associated with OS following lenvatinib treatment.

Conclusion

Lenvatinib treatment offers significant benefits in patients with good liver function in real-world practice. The various characteristics identified in this study might be helpful as clinical predictors of response to lenvatinib and survival in clinical practice. Further studies are required to address eligibility for lenvatinib treatment in CP 7 patients.

Keywords:

• lenvatinib
• tyrosine kinase inhibitor
• hepatocellular carcinoma
• Child-Pugh
• adverse events
• overall survival

Abbreviations

HCC, hepatocellular carcinoma; RECIST, response evaluation criteria in solid tumors; mRECIST, modified response evaluation criteria in solid tumors; VEGFR, vascular endothelial growth factor receptor; FGF, fibroblast growth factor; FGFR, fibroblast growth factor receptor; OS, overall survival; PFS, progression-free survival; OR, objective response; ORR, objective response rate; RDI, relative dose intensity; AFP, α-fetoprotein; AFP-L3, lens culinaris agglutinin-reactive fraction of α-fetoprotein; DCP, des-gamma-carboxy prothrombin; TNM, tumor node metastasis classification; BCLC, Barcelona clinic liver cancer, CP; Child-Pugh; mALBI, modified albumin-bilirubin; ROC, receiver operating characteristic; AUROC, area under the ROC curve.

Data Sharing Statement

The authors do not intend to share the individual de-identified participant data and the data and document will be available on the University Hospital Medical Information Network Clinical Trials Registry website (UMIN000037054).

Ethical Considerations

Written informed consent for obtaining serum and using it in future studies was obtained from all patients. The study protocol conformed to the ethical guidelines of the World Medical Association Declaration of Helsinki and was approved by the respective institutional ethics committees (approval numbers: B180400020).

Acknowledgments

The authors would like to thank all the patients and their families, as well as the investigators and staff of the participating institutions.

Disclosure

Makoto Ueno and Tatehiro Kagawa have received research funding from Eisai Co., Ltd. The authors report no other conflicts of interest in this work.