Frontline Lenvatinib Shows Superiority to Sorafenib in HCC in Real-World Setting

Lenvatinib (Lenvima) demonstrated superiority to sorafenib (Nexavar) in the first-line setting for patients with unresectable hepatocellular carcinoma (HCC), according to results of a propensity score matching analysis that was presented during the 2021 World Congress on Gastrointestinal Cancer.¹

Further, the analysis of patients with HCC, which was in a real-world setting, suggested several factors that had possible predictive value for response to lenvatinib.

Lenvatinib was suggested to be noninferior to sorafenib as a frontline treatment for patients with unresectable HCC in the open-label phase 3 REFLECT noninferiority trial (NCT01761266). Investigators from Italy and Japan sought to determine which agent was superior in a real-world setting.

A total of 92 patients were treated with lenvatinib and 92 with sorafenib. Those treated with lenvatinib experienced a greater survival benefit than those treated with sorafenib. The median overall survival was 15.2 months with lenvatinib and 10.5 months with sorafenib, accounting for a 36% reduction in risk of death (HR, 0.64; 95% CI, 0.45-0.91; P = .0156).

The progression-free survival was 7.0 months with lenvatinib compared with 4.5 months with sorafenib (HR, 0.71; 95% CI, 0.50-0.98; P = .0446).

The majority of patients in each arm experienced at least 1 adverse event of any grade. Toxicities were reported in 96.4% of the lenvatinib arm, and 51.6% of events were higher than grade 2. Adverse events were observed in 94.6% of patients in the sorafenib arm, with 50.4% higher than grade 2.

Sorafenib was associated with a higher degree of hand-foot skin reaction than lenvatinib (48.3% vs 23.6%). Grade 3 or higher hand-foot-skin reaction was reported in 26.8% of patients treated with sorafenib and 4.3% of patients treated with lenvatinib.

On the other hand, lenvatinib was associated with more hypertension (54.8% vs 33.4% with sorafenib) and fatigue (57.0% vs 35.5%, respectively). Grade 3 or higher hypertension was observed in 11.8% of patients treated with lenvatinib and 15.1% of patients treated with sorafenib. Grade 3 or higher fatigue was noted in 17.2% and 12.9% of patients treated with lenvatinib and sorafenib, respectively.

A number of factors were found to be associated with a response to lenvatinib, including albumin level, ECOG performance status, portal vein thrombosis, hepatitis C virus negativity, aspartate aminotransferase, and alkaline phosphatase. Barcelona Clinic Liver Cancer stage, bilirubin, and eosinophil count were all associated with sorafenib.

However, further research is required to validate these predictive factors of response.

References

1. Rimini M, Tada T, Lonardi S, et al. Comparison of propensity score matching analysis of sorafenib and lenvatinib as first line therapy in uHCC: a multi-center analysis. Presented at: 2021 World Congress on Gastrointestinal Cancer; June 30-July 2, 2021; Virtual. Abstract P-40.
2. Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163-1173. doi:10.1016/S0140-6736(18)30207-1