Lenvatinib Monotherapy Demonstrates Efficacy in the First Line for HCC

In a retrospective, real-world analysis of patients with unresectable hepatocellular carcinoma in the United States, investigators observed that lenvatinib alone was effective as first-line treatment.

In a retrospective, real-world analysis of patients with unresectable hepatocellular carcinoma (uHCC) in the United States, investigators observed that lenvatinib (Lenvima) alone was effective as first-line treatment.1

“Real-world data are essential to assess if this efficacy translates into effectiveness in clinical practice,” the authors wrote in their background. “The main objective of our real-world data study was to assess clinical characteristics and effectiveness of lenvatinib among patients treated in United states clinical practices.”

With a median follow-up of 9 months after patients were diagnosed with HCC, the median progression-free survival (PFS) and overall survival (OS) with lenvatinib, an oral multikinase inhibitor, were not reached in the subgroups of patients with Child-Pugh class A (n = 104) and B (n = 91) or in the overall cohort (n = 233).

The landmark PFS was 85% at 6 months and 65% at 12 months in the overall cohort. For patients with Child-Pugh A disease, landmark PFS was 83% and 51% at 6 and 12 months, respectively; with Child-Pugh B disease, PFS was 90% and 76%, respectively.

At 6 and 12 months, the landmark OS in the overall cohort was 92% and 73%, respectively. Child-Pugh A landmark OS was 96% and 73% and Child-Pugh B was 90% and 78% at 6 and 12 months, respectively.

The provider-reported best response was complete response (CR) in 21% of patients in the overall cohort, partial response (PR) in 44%, and stable disease (SD) in 26%. Eight percent of patients in this cohort experienced disease progression and 1% of patients had unknown response.

Based on RECIST 1.1 (n = 125), the best response was CR in 16%, PR in 54%, and SD in 26%; 5% had disease progression. For the 11 patients evaluated with mRECIST, best response was CR in 73%, PR in 0%, and SD in 18%; 9% experienced disease progression.

At initiation, the median dose of lenvatinib was 12 mg, which was the dose used in the registration trial that led to lenvatinib’s approval. Lenvatinib was approved as monotherapy in patients with uHCC in August 2018 based on the phase 3 REFLECT trial (NCT01761266).2 Nine percent of patients required a dose reduction in the real-world data analysis.

The median duration of treatment with the study drug was 6.7 months after a median follow-up period of 9.1 months. Those remaining on lenvatinib by the end of follow-up made up 61% of patients.

After treatment with lenvatinib, the median time to second-line therapy was 7.8 months. There were 32 patients who started second-line treatment, with the most common being immunotherapy in 50%, sorafenib (Nexavar) in 31%, and regorafenib (Stivarga) in 9%.

Of the 233 patients treated with lenvatinib in the first line, a majority were Barcelona Clinical Liver Cancer stage B or C at initiation (28.8% and 43.8%, respectively). There were 18.5% of patients who exhibited portal vein invasion, of which 7% had main portal vein involvement.

Furthermore, 44.6% were reported to be Child-Pugh class A at initiation and 39.1% were Child-Pugh class B. Hepatitis C was reported in 36.1% of patients and 15.5% were reported to have hepatitis B. Patients with alcohol-related liver disease made up 28.3% of the overall cohort and 13.7% had nonalcoholic steatohepatitis.

Prior to initiation of lenvatinib, 20.2% of patients had procedures, the most common of which were transarterial chemoembolization in 10.7% and radiofrequency ablation in 8%.

The investigators included patients who started lenvatinib monotherapy in the first line between August 16, 2018 and September 30, 2019 in this retrospective analysis. Patients had to be 18 years or older with confirmed uHCC, and an ECOG performance status of 0 or 1.

If patients had evidence of other malignant neoplasms before their diagnosis of HCC, and if they had been disease free for over 3 years at the time of starting lenvatinib, they were not included in these data. Those who had liver transplantation at any point were also excluded.

For this analysis, the investigators recruited 75 physicians; 41.3% were from cancer centers, 37.3% were from private hospitals, and 17.3% were from academic teaching hospitals. They used data extracted from electronic health records of individual patients from the participating prescribing physicians.

No safety data were collected for this analysis.


1. Singal AG, Nagar S, Hitchens A, Iyer S. Real-world effectiveness of lenvatinib monotherapy among unresectable hepatocellular carcinoma patients treated in United States clinical practices. Poster presented at: 2021 Gastrointestinal Cancers Symposium; January 15-17, 2021; virtual. Abstract 273.

2. FDA approves lenvatinib for unresectable hepatocellular carcinoma. News release. FDA, Published August 16, 2018. Accessed January 15, 2021. https://bit.ly/3snAcjT